Ontology highlight
ABSTRACT: Background
Lynch syndrome (LS) is an autosomal dominant cancer predisposition condition caused by germline heterozygous mutations in mismatch repair (MMR) genes. However, as one of the MMR genes, PMS2 mutation-induced LS-associated ovarian cancer (LSAOC) has rarely been reported.Methods
Next-generation sequencing (NGS) or Sanger sequencing was used to detect the genetic status of one family including four generations with 16 members. Then, quantitative real-time PCR (qPCR), western blotting, immunohistochemistry (IHC) staining, and Swiss-Model software were used to identify the function of the PMS2 mutation.Results
Five individuals [I-1, II-1, II-2, II-4, and III-2 (proband)] suffered from LS-associated cancers, for example, colon cancer, gastric cancer, and ovarian cancer, with the age of onset ranging from 39 to 70 years old. A PMS2 germline heterozygous mutation (c.943C>T) was confirmed in three members [II-9, III-2, and IV-1] by gene sequencing. In addition, this PMS2 mutation was verified by qPCR, western blotting, and IHC, and a dramatic change with partial loss of the C-terminal domain in an ?-helix might be exhibited.Conclusion
Carrying PMS2 germline mutations (c.943C>T) confers an extremely high susceptibility of suffering from LS-associated cancers. Thus, close clinical monitoring and prophylactic surgery is highly recommended to help reduce the morbidity and mortality of LS-associated cancers.
SUBMITTER: Guo X
PROVIDER: S-EPMC6565568 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Guo Xiaoqing X Wu Weimin W Gao Hao H Li Xiaofeng X He Qizhi Q Zhu Yong Y Liu Na N
Molecular genetics & genomic medicine 20190505 6
<h4>Background</h4>Lynch syndrome (LS) is an autosomal dominant cancer predisposition condition caused by germline heterozygous mutations in mismatch repair (MMR) genes. However, as one of the MMR genes, PMS2 mutation-induced LS-associated ovarian cancer (LSAOC) has rarely been reported.<h4>Methods</h4>Next-generation sequencing (NGS) or Sanger sequencing was used to detect the genetic status of one family including four generations with 16 members. Then, quantitative real-time PCR (qPCR), weste ...[more]