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The genetic landscape of 87 ovarian germ cell tumors
E. Van Nieuwenhuysen, P. Busschaert, P. Neven, SN. Han, P. Moerman, M. Liontos, M. Papaspirou, J. Kupryjanczyk, C. Hogdall, E. Hogdall, A. Oaknin, A. Garcia, S. Mahner, F. Trillsch, D. Cibula, F. Heitz, N. Concin, P. Speiser, H. Salvesen, J....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- dospělí MeSH
- fosfatidylinositol-3-kinasy genetika metabolismus MeSH
- fosfohydroláza PTEN genetika metabolismus MeSH
- germinální a embryonální nádory genetika patologie MeSH
- lidé MeSH
- lidské chromozomy genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutační analýza DNA metody MeSH
- nádory vaječníků genetika patologie MeSH
- protoonkogenní proteiny c-akt genetika metabolismus MeSH
- protoonkogenní proteiny c-kit genetika MeSH
- protoonkogenní proteiny p21(ras) genetika MeSH
- sekvenování exomu metody MeSH
- signální transdukce genetika MeSH
- variabilita počtu kopií segmentů DNA genetika MeSH
- zárodečné mutace genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Ovarian germ cell tumors (OGCT) are rare gynecological neoplasms, mostly affecting children and young women. The underlying molecular genetic background of these tumors is poorly characterized. METHODS: We analyzed somatic copy number aberration (CNA) profiles in 87 OGCT tumors and performed whole exome sequencing (WES) on 24 OGCT tumor and matched germline samples to further elucidate their molecular genetic landscape. RESULTS: The overall mutation rate was very low in OGCT compared to other human cancers, with an average of 0.05 mutations per Mb, consistent with their embryological origin. We identified recurrent mutations in KIT and KRAS, while CNA profiling revealed frequent focal amplifications affecting PIK3CA and AKT1 in yolk sac tumors, recurrent focal deletions affecting chromosomal regions 1p36.32, 2q11.1, 4q28.1, 5p15.33, 5q11.1 and 6q27, as well as gains in chromosome 12p that were present in all tumors, except for pure immature teratomas. CONCLUSION: We here present the first whole exome sequencing data and to our knowledge the largest CNA study in OGCT. We confirmed that earlier reported KIT mutations were frequent in dysgerminomas and mixed forms with a dysgerminoma component, whereas chromosome 12p gains were present in all histological subtypes except pure immature teratomas. We detected recurrent KRAS mutations, recurrent focal deletions and an enrichment in the PI3K/AKT/PTEN pathway in yolk sac tumors. Several of these aberrations involve targetable pathways, offering novel treatment modalities for OGCT.
Center for Cancer Biology VIB Herestraat 49 bus 912 3000 Leuven Belgium
Department of Gynecology and Obstetrics Kliniken Essen Mitte Henricistrasse 92 45136 Essen Germany
Department of Obstetrics and Gynecology University Hospitals Leuven Leuven Belgium
Department of Pathology Herlev University Hospital Herlev Ringvej 75 DK 2730 Herlev Denmark
Department of Pathology University Hospitals Leuven Herestraat 49 3000 Leuven Belgium
Laboratory for Translational Genetics Department of Oncology KU Leuven Belgium
Medical Oncology Department Vall d'Hebron University Hospital Barcelona Spain
Pathology Department Vall d'Hebron University Hospital P Vall d'Hebron 119 129 08035 Barcelona Spain
Vall d'Hebron Institute of Oncology VHIO P Vall d'Hebron 119 129 08035 Barcelona Spain
Citace poskytuje Crossref.org
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- $a Van Nieuwenhuysen, Els $u Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium; Division of Gynaecological Oncology, Leuven Cancer Institute, Kuleuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: Els.vannieuwenhuysen@uzleuven.be.
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- $a The genetic landscape of 87 ovarian germ cell tumors / $c E. Van Nieuwenhuysen, P. Busschaert, P. Neven, SN. Han, P. Moerman, M. Liontos, M. Papaspirou, J. Kupryjanczyk, C. Hogdall, E. Hogdall, A. Oaknin, A. Garcia, S. Mahner, F. Trillsch, D. Cibula, F. Heitz, N. Concin, P. Speiser, H. Salvesen, J. Sehouli, D. Lambrechts, I. Vergote,
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- $a BACKGROUND: Ovarian germ cell tumors (OGCT) are rare gynecological neoplasms, mostly affecting children and young women. The underlying molecular genetic background of these tumors is poorly characterized. METHODS: We analyzed somatic copy number aberration (CNA) profiles in 87 OGCT tumors and performed whole exome sequencing (WES) on 24 OGCT tumor and matched germline samples to further elucidate their molecular genetic landscape. RESULTS: The overall mutation rate was very low in OGCT compared to other human cancers, with an average of 0.05 mutations per Mb, consistent with their embryological origin. We identified recurrent mutations in KIT and KRAS, while CNA profiling revealed frequent focal amplifications affecting PIK3CA and AKT1 in yolk sac tumors, recurrent focal deletions affecting chromosomal regions 1p36.32, 2q11.1, 4q28.1, 5p15.33, 5q11.1 and 6q27, as well as gains in chromosome 12p that were present in all tumors, except for pure immature teratomas. CONCLUSION: We here present the first whole exome sequencing data and to our knowledge the largest CNA study in OGCT. We confirmed that earlier reported KIT mutations were frequent in dysgerminomas and mixed forms with a dysgerminoma component, whereas chromosome 12p gains were present in all histological subtypes except pure immature teratomas. We detected recurrent KRAS mutations, recurrent focal deletions and an enrichment in the PI3K/AKT/PTEN pathway in yolk sac tumors. Several of these aberrations involve targetable pathways, offering novel treatment modalities for OGCT.
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- $a Busschaert, Pieter $u Laboratory for Translational Genetics, Department of Oncology, KU Leuven, Belgium; Center for Cancer Biology, VIB, Herestraat 49, bus 912, 3000 Leuven, Belgium. Electronic address: Pieter.busschaert@kuleuven.be.
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- $a Liontos, Michalis $u Division of Clinical Therapeutics, Oncology Department, National and Kapodistrian Univerity of Athens, 80 Vas Sofias Ave, 11528 Athens, Greece.
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- 700 1_
- $a Kupryjanczyk, Jolanta $u Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Roentena 5, 02-781 Warsaw, Poland. Electronic address: jkupry@coi.waw.pl.
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- $a Hogdall, Claus $u Department of Gynecology, The Juliane Marie Centre, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: Claus.hoegdall@regionh.dk.
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