乳腺癌分子分型与遗传基因变异谱关系的初步探讨

A Preliminary Study on the Relationship between Molecular Typing and Genetic Variation Spectrum of Breast Cancer

目的:探讨不同乳腺癌分子分型患者遗传基因变异谱,为乳腺癌患者的个体化管理提供参考。方法:本研究主要通过提取66例乳腺癌患者的外周血白细胞DNA,采用杂交捕获的方法构建DNA文库,主要涵盖ATM、BRCA1、BRCA2、CDH1、PALB2等53个基因,在Nextseq 550测序仪进行高通量测序检测,并对检测结果依据ACMG指南进行判读。结果:66例乳腺癌中Luminal A型22例,Luminal B型25例,HER2过表达型5例,三阴型14例,共检出108个基因变异。Luminal A和Luminal B型乳腺癌主要发生BRCA1、BRCA2、错配修复基因MLH1/MSH2/MSH6/PMS2等基因变异,致病性变异以BRCA1/2为主;HER2过表达型乳腺癌主要发生错配修复基因变异,但未检出致病性变异;三阴型乳腺癌主要发生BRCA2和错配修复基因变异,含一例MSH2致病性变异,未发现BRCA1致病性变异。结论:BRCA1/2基因是Luminal型乳腺癌最主要的遗传易感基因,而错配修复基因可能与HER2过表达型和三阴型乳腺癌遗传易感相关。

Objective:To provide reference for individual management of breast cancer patients by analyzing the genetic variation spectrum of different breast cancer molecular types.Methods:In this study,the peripheral blood leukocyte DNA of 66 breast cancer patients was extractedtoconstructthe DNA library by hybrid capture method,covering53 genes including ATM,BRCA1,BRCA2,CDH1,PALB2,etc.Sequencing was performed on the Nextseq 550 platform,and the detection results were further interpreted according to the ACMG guidelines.Results:Among the 66 cases,there were 22 cases of Luminal A,25 cases of Luminal B,5 cases of HER2 overexpressed,and 14 cases of triple negative.A total of 109 gene variants were found.The most prevalent variants of Luminal A and Luminal B breast cancers areBRCA1,BRCA2,and mismatch repair genes such as MLH1/MSH2/MSH6/PMS2,and the majority of pathogenic variation isBRCA1/2.Mismatch repair gene variation is majorof HER2 overexpressed breast cancer,but no pathogenicity variation was found.BRCA2 and mismatch repair gene mutations were major in triple-negative breast cancer,including one case with MSH2 pathogenic mutation,but no BRCA1/2 pathogenic mutation was found.Conclusion:BRCA1/2 gene is the main genetic susceptibility gene of Luminal type breast cancer,while HER2 overexpression type and triple negative type breast cancer may be more closely related to mismatch repair gene.