A1 Journal article (refereed)
WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas (2021)
Aavikko, M., Kaasinen, E., Andersson, N., Pentinmikko, N., Sulo, P., Donner, I., Pihlajamaa, P., Kuosmanen, A., Bramante, S., Katainen, R., Sipilä, L. J., Martin, S., Arola, J., Carpén, O., Heiskanen, I., Mecklin, J.-P., Taipale, J., Ristimäki, A., Lehti, K., . . . Aaltonen, L. A. (2021). WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas. Human Molecular Genetics, 30(24), 2429-2440. https://doi.org/10.1093/hmg/ddab206
JYU authors or editors
Publication details
All authors or editors: Aavikko, Mervi; Kaasinen, Eevi; Andersson, Noora; Pentinmikko, Nalle; Sulo, Päivi; Donner, Iikki; Pihlajamaa, Päivi; Kuosmanen, Anna; Bramante, Simona; Katainen, Riku; et al.
Journal or series: Human Molecular Genetics
ISSN: 0964-6906
eISSN: 1460-2083
Publication year: 2021
Publication date: 19/07/2021
Volume: 30
Issue number: 24
Pages range: 2429-2440
Publisher: Oxford University Press (OUP)
Publication country: United Kingdom
Publication language: English
DOI: https://doi.org/10.1093/hmg/ddab206
Publication open access: Openly available
Publication channel open access: Partially open access channel
Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/79706
Abstract
We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas.
To assess the genetic susceptibility and understand the novel phenotype we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization, and organoid culture.
We detected a heterozygous deletion at the cystic fibrosis locus (7q31.2) perfectly segregating with the intestinal tumor predisposition in the family. The deletion removes a topologically associating domain (TAD) border between CFTR and WNT2, aberrantly activating WNT2 in the intestinal epithelium. These consequences suggest that the deletion predisposes to small intestinal neuroendocrine tumors and small and large intestinal adenocarcinomas, and reveals the broad tumorigenic effects of aberrant WNT activation in the human intestine.
Keywords: cancerous diseases; bowel cancer; cancer of the large intestine; adenocarcinoma; hereditary predisposition; hereditary diseases; genetic factors
Contributing organizations
Ministry reporting: Yes
Reporting Year: 2021
JUFO rating: 2