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Multigene Panel Testing Increases the Number of Loci Associated with Gastric Cancer Predisposition.

Authors :
Tedaldi, Gianluca
Pirini, Francesca
Tebaldi, Michela
Zampiga, Valentina
Cangini, Ilaria
Danesi, Rita
Arcangeli, Valentina
Ravegnani, Mila
Abou Khouzam, Raefa
Molinari, Chiara
Oliveira, Carla
Morgagni, Paolo
Saragoni, Luca
Bencivenga, Maria
Ulivi, Paola
Amadori, Dino
Martinelli, Giovanni
Falcini, Fabio
Ranzani, Guglielmina Nadia
Calistri, Daniele
Source :
Cancers; Sep2019, Vol. 11 Issue 9, p1340-1340, 1p
Publication Year :
2019

Abstract

The main gene involved in gastric cancer (GC) predisposition is CDH1, the pathogenic variants of which are associated with diffuse-type gastric cancer (DGC) and lobular breast cancer (LBC). CDH1 only explains a fraction (10–50%) of patients suspected of DGC/LBC genetic predisposition. To identify novel susceptibility genes, thus improving the management of families at risk, we performed a multigene panel testing on selected patients. We searched for germline pathogenic variants in 94 cancer-related genes in 96 GC or LBC Italian patients with early-onset and/or family history of GC. We found CDH1 pathogenic variants in 10.4% of patients. In 11.5% of cases, we identified loss-of-function variants in BRCA1, BRCA2, PALB2, and ATM breast/ovarian cancer susceptibility genes, as well as in MSH2, PMS2, BMPR1A, PRF1, and BLM genes. In 78.1% of patients, we did not find any variants with clear-cut clinical significance; however, 37.3% of these cases harbored rare missense variants predicted to be damaging by bioinformatics tools. Multigene panel testing decreased the number of patients that would have otherwise remained genetically unexplained. Besides CDH1, our results demonstrated that GC pathogenic variants are distributed across a number of susceptibility genes and reinforced the emerging link between gastric and breast cancer predisposition. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20726694
Volume :
11
Issue :
9
Database :
Complementary Index
Journal :
Cancers
Publication Type :
Academic Journal
Accession number :
138961535
Full Text :
https://doi.org/10.3390/cancers11091340