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Cutaneous apocrine carcinoma is an extreme rare malignancy derived from a sweat gland. Histologically sweat gland cancers resemble metastatic mammary apocrine carcinomas, but the genetic landscape remains poorly understood. Here, we report a rare metastatic case with a PALB2 aberration identified previously as a familial susceptibility gene for breast cancer in the Finnish population. As PALB2 exhibits functions in the BRCA1/2-RAD51-dependent homologous DNA recombination repair pathway, we sought to use ex vivo functional screening to explore sensitivity of the tumor cells to therapeutic targeting of DNA repair. Drug screening suggested sensitivity of the PALB2 deficient cells to BET-bromodomain inhibition, and modest sensitivity to DNA-PKi, ATRi, WEE1i and PARPi. A phenotypic RNAi screen of 300 DNA repair genes was undertaken to assess DNA repair targeting in more detail. Core members of the HR and MMEJ pathways were identified to be essential for viability of the cells. RNAi inhibition of RAD52-dependent HR on the other hand potentiated the efficacy of a novel BETi ODM-207. Together these results describe the first ever CAC case with a BRCAness genetic background, evaluate combinatorial DNA repair targeting, and provide a data resource for further analyses of DNA repair targeting in PALB2 deficient cancers.
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INTRODUCTION: Apocrine sweat gland carcinomas (ASGCs) are rare malignant skin tumours in dogs and humans. The literature published so far focuses mostly on the clinico-epidemiological aspect of these tumours, but little is known about their pathogenesis. In this study we aimed to determine whether the p53 gene is involved in the carcinogenesis of the apocrine sweat gland in dogs and whether ultraviolet radiation (UV) is related to it. MATERIAL AND METHODS: Forty canine ASGCs were submitted to laser capture microdissection to isolate neoplastic cells, from which DNA was subsequently extracted. PCR amplification and sequencing of p53 exons 2-8 was then performed, followed by computer analysis of the obtained sequences. RESULTS: Sixteen mutations within the p53 gene were found in 13 tumours. The mutations involved C â T, T â C, G â A, and CC â TT transitions, C â G transversion and adenine deletion, which are gene alteration types known to be related to UV radiation in the process of skin carcinogenesis in humans. Six of the thirteen tumour cases displayed the C â T transitions in the same location in exon 4 and three of the thirteen cases displayed T â C in the same location in exon 5. CONCLUSION: The results of the present study indicate both the participation of the p53 gene and the influence of UV radiation in the formation of ASGCs in dogs.
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INTRODUCTION: Primary apocrine sweat gland carcinoma (PASGC) is a rare subtype of sweat gland carcinoma, mostly occurring in the apocrine-dense regions such as the axilla, areola, and scalp. PRESENTATION OF CASE: An 83-year-old woman developed a red elevating mass on her left axilla, without palpable axillary lymph nodes. Excision biopsy revealed that the tumor was PASGC. Additional wide resection and sentinel lymph node biopsy (SLNB) were performed without any adjuvant therapy. One year after the surgical procedure, the patient did not show any evidence of recurrence and axillary surgical complications. DISCUSSION: As PASGC arising in the axilla can progress aggressively, differential diagnosis is essential. Previous reports have shown the usefulness of SLNB, but the axillary management for patients with clinically node negative PASGC has not been established because of its rarity. Especially in axillary cases, to identify the true sentinel lymph nodes is sometimes considered inaccurate because the lymphatic flow is complicated in the axilla. CONCLUSION: Although SLNB in sweat gland carcinoma has believed safety and been performed, this is the first axillary PASGC case that was performed SLNB. Careful follow-up is needed.
RESUMEN
INTRODUCTIONS: Sweat gland carcinoma is very rare with a reported incidence of less than 0.005% of all tumour specimens resected surgically (Tulenko and Conway, 1965) [1]. CASE REPORT: A sixty year old male patient presented to us with a solitary swelling over the left chest wall since two months. DISCUSSION: Cutaneous apocrine gland carcinoma, a subtype of sweat gland carcinoma, is a very rare malignant neoplasm arising in areas of high apocrine sweat gland density. The variability of the histological features even in the same tumour, and its rarity, have contributed to some confusion regarding the classification of sweat gland carcinoma. CONCLUSIONS: Sweat gland carcinomas are a rare group of tumours with potential for local destruction as well as distant metastasis. Wide surgical excision along with regional lymph node dissection in the presence of clinically positive nodes is the recommended treatment. However, a frequent follow up is essential to detect early recurrence as well as distant metastasis.