Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma.
Adult
Aged
Aged, 80 and over
Carcinoma, Endometrioid
/ genetics
Carcinosarcoma
/ classification
Cluster Analysis
DNA Copy Number Variations
/ genetics
DNA Methylation
DNA Polymerase II
/ genetics
DNA Repair-Deficiency Disorders
/ genetics
Decision Trees
Epithelial-Mesenchymal Transition
/ genetics
Female
Genital Neoplasms, Female
/ genetics
High-Throughput Nucleotide Sequencing
Humans
INDEL Mutation
Microsatellite Instability
Middle Aged
Mutation
Neoplasms, Cystic, Mucinous, and Serous
/ genetics
Ovarian Neoplasms
/ classification
Peritoneal Neoplasms
/ genetics
Poly-ADP-Ribose Binding Proteins
/ genetics
Polymorphism, Single Nucleotide
RNA, Messenger
/ metabolism
Sequence Analysis, DNA
Transcriptome
Uterine Neoplasms
/ classification
Young Adult
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
31 10 2019
31 10 2019
Historique:
received:
25
03
2019
accepted:
11
10
2019
entrez:
2
11
2019
pubmed:
2
11
2019
medline:
4
3
2020
Statut:
epublish
Résumé
Carcinosarcoma (CS) of the uterus or ovary is a rare, aggressive and biphasic neoplasm composed of carcinoma and sarcoma elements. Previous genomic studies have identified the driver genes and genomic properties associated with CS. However, there is still no molecular subtyping scheme with clinical relevance for this disease. Here, we sequence 109 CS samples, focusing on 596 genes. We identify four molecular subtypes that resemble those observed in endometrial carcinoma: POLE-mutated, microsatellite instability, copy number high, and copy number low subtypes. These molecular subtypes are linked with DNA repair deficiencies, potential therapeutic strategies, and multiple clinicopathological features, including patient outcomes. Multi-regional comparative sequencing reveals genomic alteration-independent CS cell differentiation. Transcriptome and DNA methylome analyses confirm epithelial-mesenchymal transition as a mechanism of sarcoma differentiation. The current study thus provides therapeutic possibilities for CS as well as clues to understanding the molecular histogenic mechanism of its development.
Identifiants
pubmed: 31672974
doi: 10.1038/s41467-019-12985-x
pii: 10.1038/s41467-019-12985-x
pmc: PMC6823358
doi:
Substances chimiques
Poly-ADP-Ribose Binding Proteins
0
RNA, Messenger
0
DNA Polymerase II
EC 2.7.7.7
POLE protein, human
EC 2.7.7.7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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