文章：

中国乳腺癌患者生殖系突变双重杂合性研究

Double Heterozygosity for Germline Mutations in Chinese Breast Cancer Patients

原文发布日期：15 July 2024

DOI: 10.3390/cancers16142547

类型: Article

开放获取: 是

英文摘要：

Double pathogenic mutations occurring in an individual are considered a rare event. The introduction of a multiple-gene panel at Hong Kong Hereditary Breast Cancer Family Registry has allowed the identification of pathogenic variants in multiple genes, providing more information on clinical management and surveillance to the proband and their family members. Breast cancer patients who are double heterozygous (DH) for different hereditary breast and ovarian cancer syndrome (HBCO)-related genes were identified from a cohort of 3649 Chinese patients. Nine patients (0.25%) were observed to have germline DH mutations inATM,BRCA1,BRCA2,BRIP1,CDH1,CHEK2,MSH6,PALB2, andTP53. Three probands were diagnosed with unilateral breast cancer, two patients were diagnosed with bilateral breast cancer, and four patients had multiple primary cancers. The median age for breast cancer diagnosis was an early age of 36 years. Chinese DH carriers did not show worse phenotypes or have a significantly downhill clinical presentation. However, seven out of nine (77.8%) of our DH carriers harbored aBRCA1mutation, and four of them (44.4%) developed bilateral breast cancer, suggesting Chinese DH individuals may have a higher chance of having bilateral breast cancer than other populations (p= 0.0237).

摘要翻译： 

个体携带双重致病性基因突变被视为罕见事件。香港遗传性乳腺癌家族登记处引入多基因检测组合，实现了对多个基因中致病性变异的识别，为患者及其家庭成员提供了更多关于临床管理和监测的信息。本研究从3649例中国乳腺癌患者队列中，识别出在不同遗传性乳腺癌-卵巢癌综合征相关基因上呈双重杂合状态的患者。共发现9例患者（0.25%）在ATM、BRCA1、BRCA2、BRIP1、CDH1、CHEK2、MSH6、PALB2和TP53基因中存在胚系双重突变。其中3例先证者诊断为单侧乳腺癌，2例为双侧乳腺癌，4例患有多原发癌。乳腺癌诊断中位年龄较早，为36岁。中国双重突变携带者并未表现出更严重的表型或显著的临床恶化趋势。然而，9例双重突变携带者中有7例（77.8%）携带BRCA1突变，其中4例（44.4%）发展为双侧乳腺癌，提示中国双重突变个体发生双侧乳腺癌的风险可能高于其他人群（p=0.0237）。

原文链接：

Double Heterozygosity for Germline Mutations in Chinese Breast Cancer Patients