客家卵巢癌患者中和种系突变的特征：C.536 A>T可能是该人群中的一个始祖突变。

The Features of and Germline Mutations in Hakka Ovarian Cancer Patients: C.536 A>T Maybe a Founder Mutation in This Population.

作者信息

Luo Yu, Wu Heming, Huang Qingyan, Rao Hui, Yu Zhikang, Zhong Zhixiong

机构信息

Department of Gynaecology, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People's Republic of China.

Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People's Republic of China.

出版信息

Int J Gen Med. 2022 Mar 10;15:2773-2786. doi: 10.2147/IJGM.S355755. eCollection 2022.

DOI:10.2147/IJGM.S355755

PMID:35300142

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8922037/

Abstract

OBJECTIVE

To investigate the frequencies of and mutations in Chinese Hakka patients with ovarian cancer.

METHODS

The protein coding regions and exon intron boundary regions of the gene were sequenced using genomic DNA isolated from the lymphocytes of patients with next-generation sequencing. The patients' family history and clinical records were collected.

RESULTS

A total of 195 patients with ovarian cancer were included in the study, and 52 distinct variants of the gene were identified. It was found that 64 patients (64/195, 32.8%) had gene mutations, including 32 patients (50.0%) with mutation, 27 patients (42.2%) with mutation, and 5 patients (7.8%) with both mutations. Furthermore, 22 pathogenic mutations were detected in 26 patients, 2 likely pathogenic variants in 2 patients, 12 variants of uncertain significance in 20 patients, and 16 likely benign variants in 24 patients. The mutations were mainly found to occur in exons 8, 14, and 17 of and exons 10, 11, 14, and 15 of . The results showed that the genes possess different mutation hotspots in different ethnic groups. In addition, recurrent mutations were noted in many patients. c.536 A>T, considered a founder mutation, was identified in 10 patients (15.63%, 10/64), followed by c.2635 G>T (6.25%, 4/64) and c.2566 T>C (6.25%, 4/64).

CONCLUSION

The c.536 A>T could be considered to be a founder mutation in this ovarian cancer population. This recurrent mutation has rarely been observed in other ethnic groups. Our findings are expected to provide valuable data for clinical consultation and for designing individualized treatment for ovarian cancer.

摘要

目的

研究中国客家卵巢癌患者中和突变的频率。

方法

使用从患者淋巴细胞中分离的基因组DNA，通过下一代测序对基因的蛋白质编码区和外显子内含子边界区域进行测序。收集患者的家族史和临床记录。

结果

本研究共纳入195例卵巢癌患者，鉴定出基因的52种不同变体。发现64例患者（64/195，32.8%）存在基因突变，其中32例患者（50.0%）发生突变，27例患者（42.2%）发生突变，5例患者（7.8%）同时发生两种突变。此外，在26例患者中检测到22个致病突变，2例患者中有2个可能的致病变体，20例患者中有12个意义未明的变体，24例患者中有16个可能的良性变体。这些突变主要发生在的第8、14和17外显子以及的第10、11、14和15外显子。结果表明，在不同种族群体中具有不同的突变热点。此外，在许多患者中发现了复发性突变。被认为是奠基者突变的 c.536 A>T在10例患者中被鉴定出（15.63%，10/64），其次是 c.2635 G>T（6.25%，4/64）和 c.2566 T>C（6.25%，4/64）。