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Background: Population studies are essential for gathering critical disease prevalence data. Automated pathogenicity assessment tools enhance the capacity to interpret and annotate large amounts of genetic data. In this study, we assessed the prevalence of cancer-associated germline variants in Russia using a semiautomated variant interpretation algorithm. Methods: We examined 74,996 Russian adults (Group 1) and 2,872 long-living individuals aged ≥ 90 years (Group 2) for variants in 28 ACMG-recommended cancer-associated genes in three steps: InterVar annotation; ClinVar interpretation; and a manual review of the prioritized variants based on the available data. Using the data on the place of birth and the region of residence, we determined the geographical distribution of the detected variants and tracked the migration dynamics of their carriers. Results: We report 175 novel del-VUSs. We detected 232 pathogenic variants, 46 likely pathogenic variants, and 216 del-VUSs in Group 1 and 19 pathogenic variants, 2 likely pathogenic variants, and 16 del-VUSs in Group 2. For each detected variant, we provide a description of its functional significance and geographical distribution. Conclusion: The present study offers extensive genetic data on the Russian population, critical for future genetic research and improved primary cancer prevention and genetic screening strategies. The proposed hybrid assessment algorithm streamlines variant prioritization and pathogenicity assessment and offers a reliable and verifiable way of identifying variants of uncertain significance that need to be manually reviewed.

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A relevant percentage of breast cancers (BCs) are tied to pathogenetic (P)/likely pathogenetic (LP) variants in predisposing genes. The knowledge of P/LP variants is an essential element in the management of BC patients since the first diagnosis because it influences surgery and subsequent oncological treatments and follow-up. Moreover, patients with metastatic BCs can benefit from personalized treatment if carriers of P/LP in BRCA1/2 genes. Multigene panels allow the identification of other predisposing genes with an impact on management. Cascade genetic testing for healthy family members allows personalized preventive strategies. Here, we review the advances and the challenges of Cancer Genetic Counseling (CGC). We focus on the area of oncology directed to hereditary BC management describing the peculiar way to lead CGC and how CGC changes over time. The authors describe the impact of genetic testing by targeted approach or universal approach on the management of BC according to the stage at diagnosis. Moreover, they describe the burden of CGC and testing and future perspectives to widely offer testing. A new perspective is needed for models of service delivery of CGC and testing, beyond formal genetic counselling. A broader genetic test can be quickly usable in clinical practice for comprehensive BC management and personalized prevention in the era of precision oncology.

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BACKGROUND: BRCA1 and BRCA2 pathogenic variants account for 90% of hereditary breast malignancies, incurring a lifetime breast cancer risk of 85% and 40-45% respectively, in affected individuals. Well-resourced health care settings offer genetic counselling and genetic screening for susceptible individuals, followed by intense breast cancer surveillance programmes for those identified at high risk of breast cancer. Such high standards of care are not available in countries with limited resources. This study assessed breast cancer surveillance behaviors among a cohort of BRCA positive Sri Lankan women. METHODS: A retrospective case review of all patients diagnosed with pathogenic variants in BRCA1 and BRCA2 genes from 2015 to 2022 at the Human Genetics Unit, Faculty of Medicine, University of Colombo was carried out followed by telephone interviews of the respondents. Patients who were not contactable, deceased, undergone bilateral mastectomy and males were excluded from the interview component of the study. Standard descriptive statistics were used to analyze the data using SPSS statistics version 25. RESULTS: Only 25 patients were diagnosed during the study period:14/25 women responded (6/25 deceased, 3/25 non-contactable; 2/25 excluded). 71.4% (10/14) had performed breast self-examination during the preceding month; 35.7% (5/14) had a clinical breast examination (CBE), and 50% (7/14) had undergone a screening/diagnostic mammogram during the last one year. 28.5% (4/14) had undergone both mammography and CBE; 21.45% (3/14) mammogram only, 7.1% (1/14) had CBE only. 42.8%(6/14) had not undergone any surveillance(mammography, CBE or MRI). None had dual screening with mammogram and MRI. 85.71% (12/14) women expressed willingness to participate in a regular screening programme if made available. CONCLUSION: Fifty percent of BRCA1/2 positive women in our study had not undergone annual imaging-based surveillance by mammography or MRI, and none had undergone annual dual screening with mammography and MRI, indicating inadequate breast cancer surveillance in this high-risk group.

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BACKGROUND: Despite decades of effort to reduce racial cancer disparities, Black people continue to die at higher rates from cancer than any other U.S. racial group. Because prevention is a key to the cost-effective and long-term control of cancer, the potential for cancer genetic counseling to play a central role in reducing racial cancer disparities is high. However, the benefits of genetic counseling are not equitable across race. Only 2% of genetic counselors self-identify as Black/African American, so most genetic counseling encounters with Black patients are racially discordant. Patients in racially discordant medical interactions tend to have poorer quality patient-provider communication and receive suboptimal clinical recommendations. One major factor that contributes to these healthcare disparities is racial bias. Drawing on findings from prior research, we hypothesize that genetic counselor providers' implicit racial prejudice will be associated negatively with the quality of patient-provider communication, while providers' explicit negative racial stereotypes will be associated negatively with the comprehensiveness of clinical discussions of cancer risk and genetic testing for Black (vs. White) patients. METHODS: Using a convergent mixed methods research design, we will collect data from at least 15 genetic counseling providers, from two different institutions, and their 220 patients (approximately equal number of Black and White patients per provider) whose appointments are for a hereditary cancer condition. The data sources will include two provider surveys, two patient surveys, video- and/or audio-recordings of genetic counseling encounters, and medical chart reviews. The recorded cancer genetic counseling in-person and telehealth encounters will be analyzed both qualitatively and quantitatively to assess the quality of patient-provider communication and the comprehensiveness of clinical discussion. Those data will be linked to pre- and post-encounter survey data and data from medical chart reviews to test our hypotheses. DISCUSSION: Findings from this multi-site study will highlight specific aspects of cancer genetic counseling encounters (patient-provider communication and clinical recommendations) that are directly associated with patient-centered outcomes (e.g., satisfaction, trust, genetic testing completion). Patient-provider communication and clinical recommendations are modifiable factors that can be integrated into current genetic counseling training curricula and thus can have immediate impact on genetic counseling training and practice.

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Because there was no genetic testing service in Cameroon, we assessed the acceptance, perceived benefits and barriers and willingness to pay for genetic cancer screening in Cameroon amongst patients with cancers. We carried out a hospital-based, cross-sectional study on adult cancer patients at the Yaoundé General Hospital and the non-Governmental Organisation Solidarity Chemotherapy between February 1, 2021, and December 31, 2021. This was a convenience sampling that included all consenting patients. Qualitative and quantitative data were analysed by Epi info version 7 and SPSS version 20. Our study included 160 (87.5% females) cancer patients, whose ages ranged from 20 to 82 years, with a mean of 49.9 ± 13.0 years. Only 11.9% had undergone some form of genetic counselling or information sessions, and most found this to be helpful in terms of increased knowledge and prevention strategies (13, 68.4%). Almost all participants (156, 97.5%) stated they will like their relatives to undergo genetic counselling. Of these, 151 (94.4%) expressed their desire for their relatives to discuss their cancer risk with a specialist. Perceived benefits of genetic testing included cancer prevention (108, 67.5%) and motivation of self-examination (81, 50.6%). Prominent possible barriers included the cost (129, 80.6%), unavailability of equipment (49, 30.6%) and anticipated anxiety (40, 25.0%). However, a majority of the participants (156, 97.5%) were willing to test for genetic mutations. One hundred and thirty-five (84.4%) participants were willing to pay for genetic testing, with the majority of them (71.8%) ready to pay between $16.7 and $100. Almost all of the participants expressed their willingness to receive cancer genetic counselling and testing but the cost became the main barrier. This pilot study will serve as a guide to the processes of establishing a cancer risk assessment clinic in Cameroon.

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BACKGROUND: A theory-guided Tailored Counseling and Navigation (TCN) intervention successfully increased cancer genetic risk assessment (CGRA) uptake among cancer survivors at increased risk of hereditary breast and ovarian cancer (HBOC). Understanding the pathways by which interventions motivate behavior change is important for identifying the intervention's active components. PURPOSE: We examined whether the TCN intervention exerted effects on CGRA uptake through hypothesized theoretical mediators. METHODS: Cancer survivors at elevated risk for HBOC were recruited from three statewide cancer registries and were randomly assigned to three arms: TCN (n = 212), Targeted Print (TP, n = 216), and Usual Care (UC, n = 213). Theoretical mediators from the Extended Parallel Process Model, Health Action Planning Approach, and Ottawa Decision Support Framework were assessed at baseline and 1-month follow-up; CGRA uptake was assessed at 6 months. Generalized structural equation modeling was used for mediation analysis. RESULTS: The TCN effects were most strongly mediated by behavioral intention alone (ß = 0.49 and 0.31) and by serial mediation through self-efficacy and intention (ß = 0.041 and 0.10) when compared with UC and TP, respectively. In addition, compared with UC, the TCN also increased CGRA through increased perceived susceptibility, knowledge of HBOC, and response efficacy. CONCLUSIONS: Risk communication and behavioral change interventions for hereditary cancer should stress a person's increased genetic risk and the potential benefits of genetic counseling and testing, as well as bolster efficacy beliefs by helping remove barriers to CGRA. System-level and policy interventions are needed to further expand access.

It is recommended that cancer survivors at increased risk for heredity seek cancer genetic risk assessment (CGRA), which includes cancer genetic counseling and genetic testing. A Tailored Counseling and Navigation (TCN) intervention successfully increased CGRA uptake among women with a history of cancer who enrolled in a randomized controlled trial. Understanding reasons for TCN's effectiveness can guide future interventions that use risk messages and behavior change techniques. We conducted mediation analyses, which enabled identification of the TCN's active components. Eligible breast and ovarian cancer survivors (n = 641) were recruited from three statewide cancer registries and were assigned to three groups: TCN, Targeted Print, and Usual Care. Mediator variables drawn from behavioral and risk communication theories were assessed at baseline and 1-month follow-up; CGRA uptake was assessed at 6 months. The strongest mediator was intention to obtain a CGRA, followed by self-efficacy, perceived risk, knowledge of hereditary breast and ovarian cancer, and perceived CGRA benefits. Risk communication and behavioral change interventions for hereditary cancer should stress a person's increased genetic risk and the potential benefits of genetic counseling and testing, as well as bolster efficacy beliefs by helping remove CGRA barriers. System-level and policy interventions are needed to further expand access.

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Transgender and nonbinary (TG/NB) individuals may engage in cancer genetic counseling for a variety of reasons, including to assess risk and obtain recommendations for cancer prevention and early detection. Barriers to TG/NB.

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Purpose: According to clinical studies, gastrointestinal stromal tumors (GISTs) are predominantly sporadic. GISTs associated with familial syndromes are very rare, and most patients exhibit wild-type KIT and platelet-derived growth factor alpha (PDGFRA). To date, GISTs associated with germline KIT pathogenic variants have been observed in only 30 kindreds worldwide. The efficacy of imatinib, a multityrosine kinase inhibitor, in patients with GIST presenting germline KIT variants has been poorly reported, and the efficacy in clinical trials of treatments with tyrosine kinase inhibitors remains unclear. Therefore, imatinib is not yet recommended for treating GIST patients with germline KIT variants. Experimental Design: We performed cancer genomic testing on samples from a 32-year-old male patient with advanced GISTs throughout the upper stomach and cutaneous hyperpigmentation to determine diagnosis and treatment strategies. Results: We detected a germline W557R pathogenic variant of KIT. The patient was diagnosed with familial multinodular GIST based on the clinical findings and familial history of malignant tumors. Treatment with imatinib resulted in long-term regression of GISTs. Conclusions: Pathogenic variants detected by cancer genome testing can be used to diagnose malignant tumors and select new therapeutic agents for patients with advanced malignancies.

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Identification of germline pathogenic variants in cancer patients is critical for treatment planning, genetic counseling, and health policymaking. However, previous estimates of the prevalence of germline etiology of pancreatic ductal adenocarcinoma (PDAC) were biased because they were based only on sequencing data of protein-coding regions of known PDAC candidate genes. To determine the percentage of patients with PDAC carrying germline pathogenic variants, we enrolled the inpatients from the digestive health clinics, hematology and oncology clinics, and surgical clinics of a single tertiary medical center in Taiwan for whole genome sequencing (WGS) analysis of genomic DNA. The virtual gene panel of 750 genes comprised PDAC candidate genes and those listed in the COSMIC Cancer Gene Census. The genetic variant types under investigation included single nucleotide substitutions, small indels, structural variants, and mobile element insertions (MEIs). In 8 of 24 (33.3%) patients with PDAC, we identified pathogenic/likely pathogenic variants, including single nucleotide substitutions and small indels in ATM, BRCA1, BRCA2, POLQ, SPINK1 and CASP8, as well as structural variants in CDC25C and USP44. We identified additional patients carrying variants that could potentially affect splicing. This cohort study demonstrates that an extensive analysis of the abundant information yielded by the WGS approach can uncover many pathogenic variants that could be missed by traditional panel-based or whole exome sequencing-based approaches. The percentage of patients with PDAC carrying germline variants might be much higher than previously expected.

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The likelihood of a diagnosis of dementia increases with a person's age, as is also the case for many cancers, including melanoma and multiple myeloma, where the median age of diagnosis is above 60 years. However, patients diagnosed with dementia are less likely to be offered invasive curative therapies for cancer. Together with analysis of diet and medication history, advanced imaging methods and genetic profiling can now indicate more about syndromes causing the neurological symptoms. Cachexia, malnutrition, dehydration, alcohol consumption, and even loneliness can all accentuate or cause the "3Ds" of dementia, delirium and depression. Many common drugs, especially in the context of polypharmacy, can cause cognitive difficulties resembling neurodegenerative disease. These syndromes may be reversed by diet, social and caregiver changes, and stopping potentially inappropriate medications (PIMs). More insidious are immune reactions to many different autoantigens, some of which are related to cancers and tumors. These can induce movement and cognitive difficulties that mimic Alzheimer's and Parkinson's diseases and other ataxias associated with aging. Paraneoplastic neurological syndromes may be reversed by directed immunotherapies if detected in their early stages but are best treated by removal of the causative tumor. A full genetic workup should be done for all individuals as soon as possible after diagnosis, to guide less invasive treatments suitable for frail individuals. While surgical interventions may be contraindicated, genetic profile guided immunotherapies, oral treatments, and radiation may be equally curative in a significant number of cancers.

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BACKGROUND: Colorectal cancer (CRC) is a highly prevalent disease in developed countries. Inherited Mendelian causes account for approximately 5% of CRC cases, with Lynch syndrome and familial adenomatous polyposis being the most prevalent forms. Scientific efforts are focused on the discovery of new candidate genes associated with CRC and new associations of phenotypes with well-established cancer-related genes. BRCA1-associated ring domain (BARD1) gene deleterious germline variants are associated with a moderate increase in the relative risk of breast cancer, but their association with other neoplasms, such as CRC, remains unclear. CASE PRESENTATION: We present the case of a 49-year-old male diagnosed with rectal adenocarcinoma whose maternal family fulfilled Amsterdam clinical criteria for Lynch syndrome. Genetic test confirmed the presence in heterozygosis of a germline pathogenic deletion of exons 8-11 in BARD1 gene. The predictive genetic study of the family revealed the presence of this pathogenic variant in his deceased cancer affected relatives, confirming co-segregation of the deletion with the disease. CONCLUSIONS: To the best of our knowledge, this is the first published work in which this BARD1 deletion is detected in a family with familial colorectal cancer type X (FCCTX) syndrome, in which the clinical criteria for Lynch syndrome without alteration of the DNA mismatch repair (MMR) system are fulfilled. Whether this incidental germline finding is the cause of familial colorectal aggregation remains to be elucidated in scientific forums. Patients should be carefully assessed in specific cancer genetic counseling units to account for hypothetical casual findings in other genes, in principle unrelated to the initial clinical suspicion, but with potential impact on their health.

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Cancer genetic testing is a revolutionary medical approach that involves the assessment of genetic markers in asymptomatic individuals to predict their future susceptibility to cancer. This paradigm shift in early detection and intervention has the potential to profoundly alter our strategies for cancer prevention and treatment. One pivotal area where genetic testing can have a significant impact is among families with a hereditary predisposition to cancer. Recent research has seen a surge in the exploration of how individuals perceive their cancer risk within the realm of cancer genetics. This proactive approach to genetic testing allows healthcare professionals to identify family members who may carry the same cancer-related genetic mutations, empowering them to make informed decisions regarding their healthcare and cancer risk management. Genetic testing for cancer-related disorders has significantly improved in accuracy and affordability, potentially revolutionizing monitoring and treatment methods. The expanding knowledge of genetic mutations associated with cancer susceptibility has driven significant progress in cancer therapy. Identifying numerous major cancer susceptibility genes has propelled predictive genetic testing, providing individuals with valuable insights into their genetic predisposition to cancer. While perceived risk plays a vital role in genetic counseling, it is equally essential to offer comprehensive information about the advantages and potential risks associated with genetic testing. Ensuring that individuals have a clear understanding of the benefits and potential drawbacks of genetic testing is imperative for making informed healthcare decisions. In our comprehensive review, researchers explored several critical aspects of genetic testing in the context of cancer, including awareness and knowledge, the communication of cancer genetic risk, genetic testing for inherited cancer syndromes, and the challenges and limitations linked to genetic testing. Through this examination, we aim to illuminate the transformative potential of genetic testing in cancer prevention and treatment.

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It is largely unknown whether genetic susceptibility contributes to tumor immune infiltration in common cancers. We systematically investigated the association between polygenic risk scores (PRSs) and tumor immune infiltration in common cancers. First, we constructed a PRS for common cancers using the risk variants identified in previous genome-wide association studies. Then, we analyzed 139 immune traits predicted by previous studies by examining gene expression data in tumor tissues from The Cancer Genome Atlas (TCGA). We applied regression analyses to evaluate the associations between PRS and immune traits for each cancer overall and stratified by stage, including 2160 pathologically confirmed cases of breast, colorectal, lung, ovarian, pancreatic, and prostate cancers in the White population. At a nominal (p < 0.05) significance level, we identified 31 significant associations between PRS and immune traits. In the analyses stratified by stage for breast, colorectal, lung adenocarcinoma, and lung squamous cell carcinoma, we identified 65 significant associations, including 56 associations that were undetected by the overall analysis. This study provides evidence for genetic risk factors affecting immune infiltration and provides novel insights into the role of genetic susceptibility in immune responses, underlying cancer development, prognosis, and the potential role of an early diagnostic or therapeutic targeting strategy.

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BACKGROUND: Prediction of contralateral breast cancer (CBC) risk is challenging due to moderate performances of the known risk factors. We aimed to improve our previous risk prediction model (PredictCBC) by updated follow-up and including additional risk factors. METHODS: We included data from 207,510 invasive breast cancer patients participating in 23 studies. In total, 8225 CBC events occurred over a median follow-up of 10.2 years. In addition to the previously included risk factors, PredictCBC-2.0 included CHEK2 c.1100delC, a 313 variant polygenic risk score (PRS-313), body mass index (BMI), and parity. Fine and Gray regression was used to fit the model. Calibration and a time-dependent area under the curve (AUC) at 5 and 10 years were assessed to determine the performance of the models. Decision curve analysis was performed to evaluate the net benefit of PredictCBC-2.0 and previous PredictCBC models. RESULTS: The discrimination of PredictCBC-2.0 at 10 years was higher than PredictCBC with an AUC of 0.65 (95% prediction intervals (PI) 0.56-0.74) versus 0.63 (95%PI 0.54-0.71). PredictCBC-2.0 was well calibrated with an observed/expected ratio at 10 years of 0.92 (95%PI 0.34-2.54). Decision curve analysis for contralateral preventive mastectomy (CPM) showed the potential clinical utility of PredictCBC-2.0 between thresholds of 4 and 12% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. CONCLUSIONS: Additional genetic information beyond BRCA1/2 germline mutations improved CBC risk prediction and might help tailor clinical decision-making toward CPM or alternative preventive strategies. Identifying patients who benefit from CPM, especially in the general breast cancer population, remains challenging.

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El Consejo Genético Oncológico (CGO) es una herramienta útil para la detección de familias con alto riesgo cáncer de mama/ ovario hereditario, con la detección de mutaciones patogénicas en los genes BRCA1 y 2. Objetivo: valorar la percepción de riesgo de cáncer en mujeres con historia personal y/o familiar de cáncer de mama/ ovario hereditario, valorar la percepción de riesgo en función de la detección de la presencia/ ausencia de una mutación patogénica en el estudio genético, y de la medida preventiva elegida tras la realización del estudio genético (seguimiento periódico o cirugía reductora de riesgo). Método: se realizó una valoración de variables sociodemográficas, clínicas y percepción de riesgo de cáncer retrospectivamente en un grupo de mujeres portadoras de mutación sometidas a estudio genético desde 1998, y prospectivamente en un grupo de mujeres sometidas a estudio genético a partir de 2015. La muestra global estaba compuesta por 262 mujeres (173 mujeres recién estudiadas y 89 mujeres portadoras de mutación estudiadas previamente). Resultados: se encontraron diferencias significativas en las mujeres que decidieron optar por una cirugía reductora de riesgo, que presentaban una percepción de riesgo mayor que las que eligieron seguimiento y se observó una disminución significativa de esa percepción tras llevar a cabo la cirugía. Conclusiones: se resalta la necesidad de evaluar la percepción de riesgo de las participantes en CGO. (AU)

The cancer genetic counseling oncology helps for detecting families at high risk for hereditary breast/ovarian cancer, due to BRCA1/2 pathogenic mutations. Objective: To assess the perception of cancer risk in women with a personal and/or family history of hereditary breast/ovarian cancer, assess the perception of risk based on the detection of the presence/absence of a pathogenic mutation, and the preventive measure chosen after completion of the study genetic (periodic follow-up or risk-reducing surgery). Method: an assessment of sociodemographic and clinical variables and perception of cancer risk was carried out retrospectively in a group of women carriers of the mutation who underwent genetic testing since 1998, and prospectively in a group of women who underwent genetic testing since 2015. The global sample was made up of 262 women (173 newly studied women and 89 previously studied mutation carrier women). Result: Significant differences were found in women who decided to opt for risk-reducing surgery, who presented a higher risk perception than those who chose follow-up, and a significant decrease in this perception was observed after carrying out the surgery. Conclusions: It is necessary to evaluate the perception of risk of the participants in CGO. (AU)

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The relationship between ubiquitin specific protease 7 (USP7) and radio-sensitivity in laryngeal squamous cell carcinoma (LSCC) has not been reported yet. Using gene chip and Label-Free mass spectrometry, we found that USP7 was significantly increased both in radioresistant LSCC patients and LSCC cells receiving irradiation. Since p53 is the most important downstream gene of USP7 and is frequently mutated in LSCC, we investigated the effects of USP7 on radioresistance of LSCC cells with or without p53 mutation. We found that knockdown of USP7 increased the radio-sensitivity in p53-mutated LSCC cells, while inhibiting the radio-sensitivity in p53-wild type cells. Knockdown of USP7 significantly inhibited the expression of the p53 and p53 pathway. Overexpressing endogenous p53 by CRISPR/dCas9 could reverse the effects of USP7 on radiosensitivity both in vitro and in vivo. Our results demonstrated the irradiation-induced USP7 led to radioresistance in p53-mutated LSCC cells but radio-sensitivity in p53-wild type cells. Therefore, the clinical application of USP7 inhibitors may improve the effects of radiotherapy in LSCC with p53 mutations and reduce the side effects on surrounding normal tissues without p53 mutation.

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MBC is a rare disease accounting for almost 1% of all cancers in men and less than 1% of breast cancer. Emerging data on the genetic drivers of predisposition for MBC are available and different risk factors have been associated with its pathogenesis. Genetic alterations, such as pathogenetic variants in BRCA1/2 and other moderate-/low-penetrance genes, along with non-genetic risk factors, have been recognized as pathogenic factors for MBC. Preventive and therapeutic implications could be related to the detection of alterations in predisposing genes, especially BRCA1/2, and to the identification of oncogenic drivers different from FBC. However, approved treatments for MBC remain the same as FBC. Cancer genetic counseling has to be considered in the diagnostic work-up of MBC with or without positive oncological family history. Here, we review the literature, reporting recent data about this malignancy with a specific focus on epidemiology, and genetic and non-genetic risk factors. We introduce the perspective of cancer genetic counseling for MBC patients and their healthy at-risk family members, with a focus on different hereditary cancer syndromes.

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Objetivos: valorar el impacto emocional de recibir los resultados del estudio genético (EG) en pacientes con antecedente oncológico personal y sospecha de síndrome hereditario, aplicando el Cuestionario Multidimensional del Impacto de la evaluación de riesgo de cáncer (MICRA). Método: 219 pacientes con diagnóstico oncológico que concurrieron a la consulta de Asesoramiento Genético Oncológico en el Instituto Alexander Fleming entre 2014 y 2019, fueron evaluados aplicando el MICRA. Resultados: Edad promedio 49,84 (42,21; 62,02), 82,2% con diagnóstico de cáncer de mama. En un 16% se halló una variante patogénica (VP). La media de los puntajes obtenidos por cada subescala fue: 5,26 (DS=4,48, rango 0-22) para Malestar Emocional (ME); 12,31 (DS 7,42 rango 0-37) para Incertidumbre (I); 16,36 (DS 4.30 rango 2-20) para Experiencias Positivas (EP) y de 34,37 (DS 10,24 rango 8-62) para la puntuación global, lo que muestra un bajo nivel de ME e I y la presencia de EP entre los pacientes. Se hallaron diferencias significativas según tipo de resultado: los portadores de VP, mostraron una modesta elevación del nivel de ME y menor puntuación en EP, respecto de aquellos que tuvieron resultados no informativos o inciertos. Sin diferencias significativas según edad, pacientes con o sin hijos, o tiempo entre la realización del estudio y la aplicación del cuestionario. Conclusiones: Recibir resultados de estudio genético no produciría un impacto psicológico adverso. Las puntuaciones altas de esta escala podrían ser usadas para identificar a pacientes con malestar emocional y ofrecerles un seguimiento psicooncológico específico (AU)

Objective: The aim of our study is to assess the emotional impact of genetic test results disclosure to patients with a personal cancer history and suspected hereditary syndrome, applying the Multidimensional Impact of Cancer Risk Assessment (MICRA) Questionnaire. Methods: two hundred nineteen patients affected with cancer, referred to the Cancer Genetic Counseling department at the Alexander Fleming Institute, between 2014 and 2019, were evaluated using the MICRA questionnaire. Results: Average age 49.84 (42,21; 62,02), 82.2% presented breast cancer. In 16% a pathogenic variant (PV) was found. The mean of the scores obtained for each subscale in the questionnaire was 5.26 (0-22, SD 4.48) for Distress (D); 12.31 (0-37, DS 7.42) for Uncertainty (U); 16.36 (2-20 SD 4.30) for Positive Experiences (PE) and 34.37 (8-62 SD 10.24) for the global score, which shows a low level of D and U and the presence of PE among the patients. Significant differences were found according to the type of result: We found modestly increased distress in PV carriers compared to patients who received uninformative or negative test results. No significant differences according to age, patients with or without children, or time between the completion of the genetic test and the application of the questionnaire. Conclusion: Genetic test disclosure does not seem to produce an adverse psychological impact. High scores on this scale could be used to identify patients with emotional distress and offer them specific psycho-oncological follow-up (AU)

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PURPOSE: Several professional societies have published guidelines for the clinical interpretation of somatic variants, which specifically address diagnostic, prognostic, and therapeutic implications. Although these guidelines for the clinical interpretation of variants include data types that may be used to determine the oncogenicity of a variant (eg, population frequency, functional, and in silico data or somatic frequency), they do not provide a direct, systematic, and comprehensive set of standards and rules to classify the oncogenicity of a somatic variant. This insufficient guidance leads to inconsistent classification of rare somatic variants in cancer, generates variability in their clinical interpretation, and, importantly, affects patient care. Therefore, it is essential to address this unmet need. METHODS: Clinical Genome Resource (ClinGen) Somatic Cancer Clinical Domain Working Group and ClinGen Germline/Somatic Variant Subcommittee, the Cancer Genomics Consortium, and the Variant Interpretation for Cancer Consortium used a consensus approach to develop a standard operating procedure (SOP) for the classification of oncogenicity of somatic variants. RESULTS: This comprehensive SOP has been developed to improve consistency in somatic variant classification and has been validated on 94 somatic variants in 10 common cancer-related genes. CONCLUSION: The comprehensive SOP is now available for classification of oncogenicity of somatic variants.

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