Identification of driver genes and somatic mutations in cell-free DNA of patients with pulmonary lymphangioleiomyomatosis.

Zhang, Li; Wang, Ming-Jie; Wang, Wei; Zhao, Jing-Ya; Wu, Jia-Liang; Liu, Yan-Pu; Zhu, Hong; Qu, Jie-Ming; Zhou, Min

Zhang, Li; Wang, Ming-Jie; Wang, Wei; Zhao, Jing-Ya; Wu, Jia-Liang; Liu, Yan-Pu; Zhu, Hong; Qu, Jie-Ming; Zhou, Min.

Afiliación

Zhang L; Department of Pulmonary and Critical Care Medicine, Shanghai Institute of Respiratory Disease, Ruijin Hospital, Shanghai Jiaotong University school of Medicine, Shanghai, China.
Wang MJ; Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Wang W; Department of Respiration, Xiangshan Traditional Chinese Medicine Hospital Huangpu District, Shanghai, China.
Zhao JY; Department of Pulmonary and Critical Care Medicine, Shanghai Institute of Respiratory Disease, Ruijin Hospital, Shanghai Jiaotong University school of Medicine, Shanghai, China.
Wu JL; Department of Respiration, Xiangshan Traditional Chinese Medicine Hospital Huangpu District, Shanghai, China.
Liu YP; Department of Respiration, Xiangshan Traditional Chinese Medicine Hospital Huangpu District, Shanghai, China.
Zhu H; Department of Respiration, Xiangshan Traditional Chinese Medicine Hospital Huangpu District, Shanghai, China.
Qu JM; Department of Pulmonary and Critical Care Medicine, Shanghai Institute of Respiratory Disease, Ruijin Hospital, Shanghai Jiaotong University school of Medicine, Shanghai, China.
Zhou M; Department of Pulmonary and Critical Care Medicine, Shanghai Institute of Respiratory Disease, Ruijin Hospital, Shanghai Jiaotong University school of Medicine, Shanghai, China.

Int J Cancer ; 146(1): 103-114, 2020 01 01.

Article en En | MEDLINE | ID: mdl-31199508

RESUMEN

Next-generation sequencing of cell-free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer-related genes. As results, log2-based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future.

Asunto(s)

Ácidos Nucleicos Libres de Células/genética; Neoplasias Pulmonares/genética; Linfangioleiomiomatosis/genética; Mutación/genética; Adulto; Proteína BRCA2/genética; ADN Tumoral Circulante/genética; ADN de Neoplasias/genética; Proteínas de Unión al ADN/genética; Femenino; Frecuencia de los Genes/genética; Genoma/genética; Genómica/métodos; Humanos; Masculino; Persona de Mediana Edad

Palabras clave

cell-free DNA; driver genes; lymphangioleiomyomatosis; next-generation sequencing; somatic mutations

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfangioleiomiomatosis / Ácidos Nucleicos Libres de Células / Neoplasias Pulmonares / Mutación Tipo de estudio: Diagnostic_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Cancer Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

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