Clinical exome sequencing identified POLB c.C1002A as a possible genetic cause in a family with hereditary cancer-predisposing syndrome

Zhenxin Zhu; Jieshi Wang; Lisha Jiang; Ling Lin; Peng Meng; Jiangman Zhao; Qingping Cai

doi:10.1016/j.cancergen.2020.06.003

Clinical exome sequencing identified POLB c.C1002A as a possible genetic cause in a family with hereditary cancer-predisposing syndrome

Cancer Genet. 2020 Jul:245:49-52. doi: 10.1016/j.cancergen.2020.06.003. Epub 2020 Jun 26.

Authors

Zhenxin Zhu¹, Jieshi Wang², Lisha Jiang³, Ling Lin³, Peng Meng³, Jiangman Zhao⁴, Qingping Cai⁵

Affiliations

¹ Gastro-intestine Surgery Department, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
² Gastrointestinal Surgery Department, the First People's Hospital of Pingdingshan, Pingdingshan, Henan, China.
³ Department of Medicine, Shanghai Zhangjiang Institue of Medical Innovation, Shanghai Biotecan Pharmaceuticals Co. Ltd., 180 Zhangheng Road, Shanghai 201204, China.
⁴ Department of Medicine, Shanghai Zhangjiang Institue of Medical Innovation, Shanghai Biotecan Pharmaceuticals Co. Ltd., 180 Zhangheng Road, Shanghai 201204, China. Electronic address: jiangzhao@biotecan.com.
⁵ Gastro-intestine Surgery Department, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China. Electronic address: caiqingping@smmu.edu.cn.

PMID: 32622089
DOI: 10.1016/j.cancergen.2020.06.003

Abstract

This study recruited a Chinese family with hereditary cancer-predisposing syndrome. To investigate the causative mutations, disease-associated exome sequencing was conducted using peripheral blood of three members with malignant disease. As a result, three variants (PLD2 c. C1951T, RAB3GAP1 c.A701G and POLB c.C1002A) came out to be the potential candidate pathogenic mutations, which were not reported before. Sanger sequencing was used to validate the candidate variant in seven healthy members of this family. The candidate variant POLB c.C1002A was proved to co-segregate with malignant diseases, which was selected through a series of filtering criteria. This study thus identified POLB c.C1002A as a potential causative variant for hereditary cancer-predisposing syndrome.

Keywords: Hereditary cancer-predisposing syndrome; Next-generation sequencing; POLB.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adult
China
DNA Polymerase beta / genetics*
Exome Sequencing / methods*
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Mutation*
Neoplastic Syndromes, Hereditary / genetics*
Pedigree

Substances

DNA Polymerase beta
POLB protein, human