Familial wild-type gastrointestinal stromal tumour in association with germline truncating variants in both SDHA and PALB2.

Whitworth, James, Casey, Ruth T, Smith, Philip S, Giger, Olivier, Martin, Jose Ezequiel, Clark, Graeme, Cook, Jaqueline, Fernando, Marlee S, Taniere, Phillipe and Maher, Eamonn R (2021) Familial wild-type gastrointestinal stromal tumour in association with germline truncating variants in both SDHA and PALB2. European journal of human genetics : EJHG. ISSN 1476-5438.

Full text not available from this repository.
Official URL: https://www.nature.com/articles/s41431-021-00862-5

Abstract

Gastrointestinal stromal tumour (GIST) is a mesenchymal neoplasm arising in the gastrointestinal tract. A rare subset of GISTs are classified as wild-type GIST (wtGIST) and these are frequently associated with germline variants that affect the function of cancer predisposition genes such as the succinate dehydrogenase subunit genes (SDHA, SDHB, SDHC, SDHD) or NF1. However, despite this high heritability, familial clustering of wtGIST is extremely rare. Here, we report a mother-son diad who developed wtGIST at age 66 and 34 years, respectively. Comprehensive genetic testing revealed germline truncating variants in both SDHA (c.1534C>T (p.Arg512*)) and PALB2 (c.3113G>A (p.Trp1038*)) in both affected individuals. The mother also developed breast ductal carcinoma in-situ at age 70 years. Immunohistochemistry and molecular analysis of the wtGISTs revealed loss of SDHB expression and loss of the wild-type SDHA allele in tumour material. No allele loss was detected at PALB2 suggesting that wtGIST tumourigenesis was principally driven by succinate dehydrogenase deficiency. However, we speculate that the presence of multilocus inherited neoplasia alleles syndrome (MINAS) in this family might have contributed to the highly unusual occurrence of familial wtGIST. Systematic reporting of tumour risks and phenotypes in individuals with MINAS will facilitate the clinical interpretation of the significance of this diagnosis, which is becoming more frequent as strategies for genetic testing for hereditary cancer becomes more comprehensive.

Item Type: Article
Subjects: QZ Pathology. Oncology
Divisions: Clinical Support > Pathology
Related URLs:
Depositing User: Mrs Yolande Brookes
Date Deposited: 25 Apr 2021 13:33
Last Modified: 25 Apr 2021 13:33
URI: http://www.repository.uhblibrary.co.uk/id/eprint/4252

Actions (login required)

View Item View Item