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Abstract：
Alterations in BRCA2, PALB2, CHEK2, and p53 genes have been identified for their association with male breast cancer in various studies. The incidence of male breast cancer in India is consistent with its global rate. The present study was carried out with an aim to evaluate the genetic alterations in male breast cancer patients from Malwa region of Punjab, India. Four male breast cancer patients belonging to different families were recruited from Guru Gobind Singh Medical College and Hospital, Faridkot, India. A total of 51 genes reported with implications in the pathogenesis of breast cancer were screened using next generation sequencing. Germline variations were found in BRCA1, BRCA2, PMS2, p53, and PALB2 genes, previously reported to be associated with MBC as well as FBC. In addition to these, 13 novel missense alterations were detected in eight genes including STK11, FZR1, PALB2, BRCA2, NF2, BAP1, BARD1, and CHEK2. Impact of these missense alterations on structure and function of protein was also analyzed through molecular dynamics simulation. Structural analysis of these single nucleotide polymorphisms (SNPs) revealed significant impact on the encoded protein functioning.
摘要：
在各种研究中，已发现BRCA2，PALB2，CHEK2和p53基因的变化与男性乳腺癌有关。印度男性乳腺癌的发病率与其全球发病率一致。本研究旨在评估旁遮普省Malwa地区男性乳腺癌患者的遗传改变，印度。来自GuruGobindSingh医学院和医院的四名属于不同家庭的男性乳腺癌患者，Faridkot,印度。使用下一代测序筛选了总共51个报道与乳腺癌发病机理有关的基因。在BRCA1，BRCA2，PMS2，p53和PALB2基因中发现了种系变异，以前报道与MBC和FBC有关。除了这些,在STK11，FZR1，PALB2，BRCA2，NF2，BAP1，BARD1和CHEK2等8个基因中检测到13个新的错义改变。还通过分子动力学模拟分析了这些错义改变对蛋白质结构和功能的影响。这些单核苷酸多态性（SNP）的结构分析揭示了对编码蛋白质功能的显着影响。
