Next Article in Journal
Local Treatment of Breast Cancer Liver Metastasis
Previous Article in Journal
Glypican 3-Targeted Therapy in Hepatocellular Carcinoma
Open AccessArticle

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

1
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy
2
Biostatistics and Clinical Trials Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy
3
Romagna Cancer Registry, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy
4
Department of Medical Oncology, Ospedale Infermi, 47923 Rimini, Italy
5
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy
6
Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal
7
Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal
8
Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal
9
Department of General Surgery, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy
10
Pathology Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy
11
Unit of Upper GI Surgery, University of Verona, 37126 Verona, Italy
12
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(9), 1340; https://doi.org/10.3390/cancers11091340
Received: 1 August 2019 / Revised: 2 September 2019 / Accepted: 8 September 2019 / Published: 11 September 2019
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. View Full-Text
Keywords: stomach neoplasms; cancer predisposition; CDH1 gene; next-generation sequencing stomach neoplasms; cancer predisposition; CDH1 gene; next-generation sequencing
Show Figures

Figure 1

MDPI and ACS Style

Tedaldi, G.; Pirini, F.; Tebaldi, M.; Zampiga, V.; Cangini, I.; Danesi, R.; Arcangeli, V.; Ravegnani, M.; Abou Khouzam, R.; Molinari, C.; Oliveira, C.; Morgagni, P.; Saragoni, L.; Bencivenga, M.; Ulivi, P.; Amadori, D.; Martinelli, G.; Falcini, F.; Ranzani, G.N.; Calistri, D. Multigene Panel Testing Increases the Number of Loci Associated with Gastric Cancer Predisposition. Cancers 2019, 11, 1340.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop