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


Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described.

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

Last updated on 2022-20-09 at 15:41