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 editorsAavikko, Mervi; Kaasinen, Eevi; Andersson, Noora; Pentinmikko, Nalle; Sulo, Päivi; Donner, Iikki; Pihlajamaa, Päivi; Kuosmanen, Anna; Bramante, Simona; Katainen, Riku; et al.

Journal or seriesHuman Molecular Genetics

ISSN0964-6906

eISSN1460-2083

Publication year2021

Publication date19/07/2021

Volume30

Issue number24

Pages range2429-2440

PublisherOxford University Press (OUP)

Publication countryUnited Kingdom

Publication languageEnglish

DOIhttps://doi.org/10.1093/hmg/ddab206

Publication open accessOpenly available

Publication channel open accessPartially open access channel

Publication is parallel published (JYX)https://jyx.jyu.fi/handle/123456789/79706


Abstract

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.


Keywordscancerous diseasesbowel cancercancer of the large intestineadenocarcinomahereditary predispositionhereditary diseasesgenetic factors


Contributing organizations


Ministry reportingYes

Reporting Year2021

JUFO rating2


Last updated on 2024-26-03 at 09:20