Hereditary diffuse gastric cancer - Pathophysiology and clinical management

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Pinheiro, H (Author) Other; Oliveira C (Author) FMUP; Seruca, R (Author) Other; Carneiro F (Author) FMUP

Journal

Title: Best Practice and Research in Clinical Gastroenterology

Vol. 28

Pages: 1055-1068

ISSN: 1521-6918

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 28 Citations

Scopus - 30 Citations

Other information

Authenticus ID: P-00A-48C

DOI: 10.1016/j.bpg.2014.09.007

Abstract (EN): Hereditary Diffuse Gastric Cancer is an autosomal dominant inherited gastric cancer syndrome caused by germline alterations in CDH1 (E-cadherin) and CTNNA1 (alpha-E-catenin) genes. Germline CDH1 alterations encompass small frameshifts, splice-site, nonsense, and missense mutations, as well as large rearrangements. Most CDH1 truncating mutations are pathogenic, and several missense CDH1 mutations have a deleterious effect on E-cadherin function. CDH1 testing should be performed in probands. Screening of at-risk individuals is indicated from the age of consent following counselling with a multidisciplinary team. In mutation-positive individuals prophylactic gastrectomy is recommended. Endoscopic surveillance is an option for those refusing/postponing gastrectomy, those with mutations of undetermined significance, and in CDH1-negative families. Ongoing research focus on the search of genetic causes other than CDH1 or CTNNA1 germline defects; assessment of the pathogenicity and penetrance of CDH1 missense mutations and identification of somatic mechanisms behind the progression from early (indolent) lesions to invasive (lethal) carcinomas.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14