Projects per year
Abstract
Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19 CRC susceptibility genes to 91 individuals of six phenotypic subgroups. Targeted NGS-based sequencing of the whole gene regions including introns of the 19 genes was used. The individuals had a family history of CRC or had a phenotype consistent with a known CRC syndrome. The purpose of the study was to demonstrate the diagnostic difficulties linked to genotype-phenotype diversity and the benefits of using a gene panel. Pathogenicity classification was carried out on 46 detected variants. In total we detected sixteen pathogenic or likely pathogenic variants and 30 variants of unknown clinical significance. Four of the pathogenic or likely pathogenic variants were found in BMPR1A in patients with unexplained familial adenomatous polyposis or atypical adenomatous polyposis, which extends the genotype-phenotype spectrum for this gene. Nine patients had more than one variant remaining after the filtration, including three with truncating mutations in BMPR1A, PMS2 and AXIN2. CNVs were found in three patients, in upstream regions of SMAD4, MSH3 and CTNNB1, and one additional individual harbored a 24.2 kb duplication in CDH1 intron1.
Original language | English |
---|---|
Pages (from-to) | 195-203 |
Journal | Familial Cancer |
Volume | 16 |
Issue number | 2 |
Early online date | 2016 Sept 30 |
DOIs | |
Publication status | Published - 2017 Apr |
Subject classification (UKÄ)
- Medical Genetics
- Cancer and Oncology
Free keywords
- Colorectal cancer
- Familial adenomatous polyposis
- FAP
- Gene panel
- Hereditary
- Lynch syndrome
Fingerprint
Dive into the research topics of 'Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing'. Together they form a unique fingerprint.-
Precision Medicine in Hereditary Cancer and Sarcoma; targeted surveillance, immunotherapy and individualized follow-up
Nilbert, M. (PI), Rambech, E. (Researcher), Jönsson, M. (Researcher), Styring, E. (Assistant supervisor), Nyström, H. (Research student) & Rosell, L. (Research student)
Project: Research
-
Precision Medicine in Hereditary Cancer and Sarcoma; targeted surveillance, immunotherapy and individualized follow-up
Nilbert, M. (PI), Nyström, H. (Research student), Rosell, L. (Research student), Jönsson, M. (Researcher), Rambech, E. (Researcher), Peterson, S. (CoI) & Styring, E. (Assistant supervisor)
2017/01/01 → 2018/12/31
Project: Research