Multigene panel testing increases the number of loci associated with gastric cancer predisposition

Gianluca Tedaldi, Francesca Pirini, Michela Tebaldi, Valentina Zampiga, Ilaria Cangini, Rita Danesi, Valentina Arcangeli, Mila Ravegnani, Raefa Abou Khouzam, Chiara Molinari, Carla Oliveira, Paolo Morgagni, Luca Saragoni, Maria Bencivenga, Paola Ulivi, Dino Amadori, Giovanni Martinelli, Fabio Falcini, Guglielmina Nadia Ranzani, Daniele Calistri

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1340
Issue number9
Publication statusPublished - Sep 2019


  • Cancer predisposition
  • CDH1 gene
  • Next-generation sequencing
  • Stomach neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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