WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas
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
Julkaistu sarjassa
Human Molecular GeneticsTekijät
Päivämäärä
2021Tekijänoikeudet
© 2021 the Authors
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.
...
Julkaisija
Oxford University Press (OUP)ISSN Hae Julkaisufoorumista
0964-6906Asiasanat
Julkaisu tutkimustietojärjestelmässä
https://converis.jyu.fi/converis/portal/detail/Publication/99087129
Metadata
Näytä kaikki kuvailutiedotKokoelmat
- Liikuntatieteiden tiedekunta [2895]
Lisätietoja rahoituksesta
This work was supported by grants from the Academy of Finland's Center of Excellence Program 2012–2017 (#250345) and 2018–2025 (#31204), the Finnish Cancer Society, the Sigrid Juselius Foundation, the Jane and Aatos Erkko Foundation. The following foundations are acknowledged for personal grants: the Helsinki University Hospital Research Grants, Finska Läkaresällskapet, the Biomedicum Helsinki Foundation, the Finnish Cancer Society, the Ida Montini Foundation, the Maud Kuistila Memorial Foundation, the Orion-Farmos Research Foundation, and the Paulo Foundation. ...Lisenssi
Samankaltainen aineisto
Näytetään aineistoja, joilla on samankaltainen nimeke tai asiasanat.
-
Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions
Wirta, Erkki-Ville; Szeto, Säde; Hänninen, Ulrika; Ahtiainen, Maarit; Böhm, Jan; Mecklin, Jukka-Pekka; Aaltonen, Lauri A.; Seppälä, Toni T. (MDPI, 2020)Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed ... -
The “unnatural” history of colorectal cancer in Lynch syndrome : lessons from colonoscopy surveillance
Ahadova, Aysel; Seppälä, Toni T.; Engel, Christoph; Gallon, Richard; Burn, John; Holinski‐Feder, Elke; Steinke‐Lange, Verena; Möslein, Gabriela; Nielsen, Maartje; ten Broeke, Sanne; Laghi, Luigi; Dominguez‐Valentin, Mev; Capella, Gabriel; Macrae, Finlay; Scott, Rodney; Hüneburg, Robert; Nattermann, Jacob; Hoffmeister, Michael; Brenner, Hermann; Bläker, Hendrik; von Knebel Doeberit,z Magnus; Sampson, Julian R.; Vasen, Hans; Mecklin, Jukka‐Pekka; Møller, Pål; Kloor, Matthias (Wiley, 2021)Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is ... -
Molecular Basis of Mismatch Repair Protein Deficiency in Tumors from Lynch Suspected Cases with Negative Germline Test Results
Olkinuora, Alisa; Gylling, Annette; Almusa, Henrikki; Eldfors, Samuli; Lepistö, Anna; Mecklin, Jukka-Pekka; Nieminen, Taina Tuulikki; Peltomäki, Päivi (MDPI AG, 2020)Some 10–50% of Lynch-suspected cases with abnormal immunohistochemical (IHC) staining remain without any identifiable germline mutation of DNA mismatch repair (MMR) genes. MMR proteins form heterodimeric complexes, giving ... -
Schizophrenia polygenic risk score and long-term success in the labour market : A cohort study
Viinikainen, Jutta; Böckerman, Petri; Hakulinen, Christian; Kari, Jaana, T.; Lehtimäki, Terho; Raitakari, Olli, T.; Pehkonen, Jaakko (Elsevier, 2022)Employment is rare among people with a schizophrenia diagnosis. Meanwhile, a genetic liability for schizophrenia may hinder labour market performance. We studied how the polygenic risk score (PGS) for schizophrenia related ... -
Rats bred for low intrinsic aerobic exercise capacity link obesity with brain inflammation and reduced structural plasticity of the hippocampus
Mäkinen, Elina; Lensu, Sanna; Honkanen, Markus; Laitinen, Paavo; Wikgren, Jan; Koch, Lauren G.; Britton, Steven L.; Kainulainen, Heikki; Pekkala, Satu; Nokia, Miriam S. (Elsevier BV, 2021)BACKGROUND Increasing evidence shows obesity and poor metabolic health are associated with cognitive deficits, but the mechanistic connections have yet to be resolved. We studied rats selectively bred for low and high ...
Ellei toisin mainittu, julkisesti saatavilla olevia JYX-metatietoja (poislukien tiivistelmät) saa vapaasti uudelleenkäyttää CC0-lisenssillä.