Heterozygous Pathogenic Nonsense Variant in the ATM Gene in a Family with Unusually High Gastric Cancer Susceptibility

Germline pathogenic variants (PVs) in the Ataxia Telangiectasia mutated ( ) gene (MIM* 607585) increase the risk for breast, pancreatic, gastric, and prostatic cancer and, to a reduced extent, ovarian and colon cancer and melanoma, with moderate penetrance and variable expressivity. We describe a fa...

Full description

Saved in:
Bibliographic Details
Published in:Biomedicines 2023-07, Vol.11 (7), p.2062
Main Authors: Guadagnolo, Daniele, Mastromoro, Gioia, Marchionni, Enrica, Germani, Aldo, Libi, Fabio, Sadeghi, Soha, Savio, Camilla, Petrucci, Simona, De Marchis, Laura, Piane, Maria, Pizzuti, Antonio
Format: Article
Language:English
Subjects:
Adenomatous polyposis coli
Age
Ataxia
Ataxia telangiectasia
Ataxia telangiectasia mutated protein
ATM
Breast cancer
cancer susceptibility
Cancer therapies
Case Report
Cell cycle
Chemotherapy
Colon cancer
DNA damage
E-cadherin
Family medical history
Gastric cancer
Genes
Genetic counseling
Genetics
Genomes
Genomics
Genotypes
Kinases
Leukemia
Lymphoma
Malignancy
Medical screening
Melanoma
MLH1 protein
MRE11 protein
MSH2 protein
MSH6 protein
Next-generation sequencing
Ovarian cancer
p53 Protein
Pancreatic cancer
Phenotypes
PTEN protein
Smad4 protein
Surveillance
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Germline pathogenic variants (PVs) in the Ataxia Telangiectasia mutated ( ) gene (MIM* 607585) increase the risk for breast, pancreatic, gastric, and prostatic cancer and, to a reduced extent, ovarian and colon cancer and melanoma, with moderate penetrance and variable expressivity. We describe a family presenting early-onset gastric cancer and harboring a heterozygous pathogenic variant. The proband had gastric cancer (age 45) and reported a sister deceased due to diffuse gastric cancer (age 30) and another sister who developed diffuse gastric cancer (age 52) and ovarian serous cancer. Next generation sequencing for cancer susceptibility genes ( , , , , , , , , , , , , , , , , , , , , , , , , and ) was performed. Molecular analysis identified the truncating c.5944C>T, p.(Gln1982*) variant in the (NM_000051.3; NP_000042.3) in the proband. The variant had segregated in the living affected sister and in the unaffected daughter of the deceased affected sister. Familial early-onset gastric cancer is an unusual presentation for -related malignancies. Individual variants may result in different specific risks. Genotype-phenotype correlations are challenging given the low penetrance and variable expressivity. Careful family history assessments are pivotal for prevention planning and are strengthened by the availability of molecular diagnoses.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines11072062