Javascript is not activated in your browser. This website needs javascript activated to work properly.
You are here

Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing

  • Anna Rohlin
  • Eva Rambech
  • Anders Kvist
  • Therese Törngren
  • Frida Eiengård
  • Ulf Lundstam
  • Theofanis Zagoras
  • Samuel Gebre-Medhin
  • Åke Borg
  • Jan Björk
  • Mef Nilbert
  • Margareta Nordling
Publishing year: 2017-04
Language: English
Pages: 195-203
Publication/Series: Familial Cancer
Volume: 16
Issue: 2
Document type: Journal article
Publisher: Kluwer

Abstract english

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.


  • Medical Genetics
  • Cancer and Oncology
  • Colorectal cancer
  • Familial adenomatous polyposis
  • FAP
  • Gene panel
  • Hereditary
  • Lynch syndrome


  • ISSN: 1389-9600
Åke Borg
Åke Borg
E-mail: ake [dot] borg [at] med [dot] lu [dot] se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2


Project manager

Familial Breast Cancer



Oncology and Pathology, MV

MV 404 C21C2