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The molecular chara...
The molecular characteristics of high-grade gastroenteropancreatic neuroendocrine neoplasms
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- Venizelos, Andreas (författare)
- University of Bergen,Haukeland University Hospital
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- Elvebakken, Hege (författare)
- Norwegian University of Science and Technology
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- Perren, Aurel (författare)
- Bern University Hospital
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- Nikolaienko, Oleksii (författare)
- Haukeland University Hospital,University of Bergen
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- Deng, Wei (författare)
- Haukeland University Hospital,University of Bergen
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- Lothe, Inger Marie B (författare)
- Oslo university hospital
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- Couvelard, Anne (författare)
- Beaujon Hospital,Hopital Bichat-Claude-Bernard AP-HP
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- Hjortland, Geir Olav (författare)
- Oslo university hospital
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- Sundlöv, Anna (författare)
- Lund University,Lunds universitet,Medicinsk onkologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medical oncology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Svensson, Johanna B (författare)
- Sahlgrenska University Hospital
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- Garresori, Harrish (författare)
- Stavanger University Hospital
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- Kersten, Christian (författare)
- Sørlandet Hospital
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- Hofsli, Eva (författare)
- Norwegian University of Science and Technology,St. Olav’s University Hospital
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- Detlefsen, Sonke (författare)
- University of Southern Denmark,Odense University Hospital
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- Krogh, Merete (författare)
- Odense University Hospital
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- Sorbye, Halfdan (författare)
- Haukeland University Hospital,University of Bergen
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- Knappskog, Stian (författare)
- Haukeland University Hospital,University of Bergen
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(creator_code:org_t)
- 2022
- 2022
- Engelska.
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Ingår i: Endocrine-Related Cancer. - 1479-6821. ; 29:1, s. 1-14
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- High-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are rare but have a very poor prognosis and represent a severely understudied class of tumours. Molecular data for HG GEP-NEN are limited and treatment strategies for the carcinoma subgroup (HG GEP-NEC) are extrapolated from small-cell lung cancer (SCLC). After pathological re-evaluation, we analysed DNA from tumours and matched blood samples from 181 HG GEP-NEN patients; 152 neuroendocrine carcinomas (NEC) and 29 neuroendocrine tumours (NET G3). Based on sequencing of 360 cancer related genes, we assessed mutations and copy number alterations (CNA). For NEC, frequently mutated genes were TP53 (64%), APC (28%), KRAS (22%) and BRAF (20%). RB1 was only mutated in 14%, but CNAs affecting RB1 were seen in 34%. Other frequent copy number losses were ARID1A (35%), ESR1 (25%) and ATM (31%). Frequent amplifications/gains were found in MYC (51%) and KDM5A (45%). While these molecular features had limited similarities with SCLC, we found potentially targetable alterations in 66% of the NEC samples. Mutations and CNA varied according to primary tumour site with BRAF mutations mainly seen in colon (49%), and FBXW7 mutations mainly seen in rectal cancers (25%). 8/152 (5.3%) NEC were microsatellite instable (MSI). NET G3 had frequent mutations in MEN1 (21%), ATRX (17%), DAXX, SETD2 and TP53 (each 14%). We show molecular differences in HG GEP-NEN, related to morphological differentiation and site of origin. Limited similarities to SCLC and a high fraction of targetable alterations indicates a high potential for better personalized treatments.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- ref (ämneskategori)
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Venizelos, Andre ...
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Elvebakken, Hege
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Perren, Aurel
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Nikolaienko, Ole ...
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Deng, Wei
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Lothe, Inger Mar ...
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Couvelard, Anne
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Hjortland, Geir ...
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Sundlöv, Anna
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Svensson, Johann ...
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Garresori, Harri ...
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Kersten, Christi ...
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Hofsli, Eva
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Detlefsen, Sonke
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Krogh, Merete
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Sorbye, Halfdan
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Knappskog, Stian
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Lunds universitet