PDF(Pubmed)
Abstract：
Cancer is a major global public health challenge, affecting both quality of life and mortality. Recent advances in genetic research have uncovered hereditary cancer syndromes (HCS) that predispose individuals to malignant neoplasms. While traditional single-gene testing has focused on high-penetrance genes, the past decade has seen a shift toward multigene panels, which facilitate the analysis of multiple genes associated with specific HCS. This approach reveals variants in less-studied gene regions and improves our understanding of cancer predisposition. In a study composed of Russian patients with clinical signs of HCS, we used a multigene hereditary cancer panel and revealed 21.6% individuals with pathogenic or likely pathogenic genetic variants. BRCA1/BRCA2 mutations predominated, followed by the CHEK2 and ATM variants. Of note, 16 previously undescribed variants were identified in the MUTYH, GALNT12, MSH2, MLH1, MLH3, EPCAM, and POLE genes. The implications of the study extend to personalized cancer prevention and treatment strategies, especially in populations lacking extensive epidemiological data, such as Russia. Overall, our research provides valuable genetic insights that give the way for further investigation and advances in the understanding and management of hereditary cancer syndromes.
摘要：
癌症是一个重大的全球公共卫生挑战。影响生活质量和死亡率。遗传研究的最新进展已发现遗传性癌症综合征（HCS），使个体易患恶性肿瘤。虽然传统的单基因检测主要集中在高外显率基因上，在过去的十年里，已经看到了向多基因面板的转变，这有助于分析与特定HCS相关的多个基因。这种方法揭示了研究较少的基因区域的变异，并提高了我们对癌症易感性的理解。在一项由具有HCS临床症状的俄罗斯患者组成的研究中，我们使用了多基因遗传性癌症组,发现21.6%的个体具有致病性或可能的致病性遗传变异.BRCA1/BRCA2突变占主导地位，其次是CHEK2和ATM变体。值得注意的是，在MUTYH中鉴定出16种以前未描述的变体，GALNT12,MSH2,MLH1,MLH3,EPCAM,和POLE基因。该研究的意义延伸到个性化的癌症预防和治疗策略，特别是在缺乏广泛流行病学数据的人群中，比如俄罗斯。总的来说,我们的研究提供了有价值的遗传见解,为进一步研究和进展遗传性癌症综合征的理解和管理提供了途径.
