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Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 20, Iss 20, p 4980 (2019)
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- Germline pathogenic variants in the CDH1 gene are a well-established cause of hereditary diffuse gastric cancer (HDGC) syndrome. The aim of this study was to characterize CDH1 mutations associated with HDGC from Chile, a country with one of the highest incidence and mortality rates in the world for gastric cancer (GC). Here, we prospectively include probands with family history/early onset of diffuse-type of GC. The whole coding sequence of the CDH1 gene was sequenced from genomic DNA in all patients, and a multidisciplinary team managed each family member with a pathogenic sequence variant. Thirty-six cases were included (median age 44 years/male 50%). Twenty-seven (75%) patients had diffuse-type GC at ≤50 years of age and 19 (53%) had first or second-degree family members with a history of HDGC. Two cases (5.5%) carried a non-synonymous germline sequence variant in the CDH1 gene: (a) The c.88C>A missense variant was found in a family with three diffuse-type GC cases; and (b) c.1531C>T a nonsense pathogenic variant was identified in a 22-year-old proband with no previous family history of HDGC. Of note, six family members carry the same nonsense pathogenic variant. Prophylactic gastrectomy in the proband’s sister revealed stage I signet-ring cell carcinoma. The finding of 1531C>T pathogenic variant in the CDH1 in proband with no previous family history of HDGC warrants further study to uncover familial clustering of disease in CDH1 negative patients. This finding may be particularly relevant in high incidence countries, such as the case in this report.
- Subjects :
- Male
0301 basic medicine
Proband
Germline
CDH1
lcsh:Chemistry
0302 clinical medicine
Medicine
Missense mutation
Family history
lcsh:QH301-705.5
Spectroscopy
Genetics
biology
Prophylactic Surgical Procedures
General Medicine
Middle Aged
Cadherins
Pedigree
Computer Science Applications
030220 oncology & carcinogenesis
Female
Hereditary diffuse gastric cancer
Adult
prophylactic gastrectomy
Article
Catalysis
Inorganic Chemistry
Young Adult
03 medical and health sciences
HDGC
Germline mutation
Antigens, CD
Gastrectomy
Neoplastic Syndromes, Hereditary
Stomach Neoplasms
cdh1
Humans
Genetic Predisposition to Disease
Physical and Theoretical Chemistry
Molecular Biology
Alleles
Genetic Association Studies
Germ-Line Mutation
Neoplasm Staging
business.industry
Organic Chemistry
Cancer
medicine.disease
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
business
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....feaae4c8726005a11cada8ab144d60a9
- Full Text :
- https://doi.org/10.3390/ijms20204980