Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Integrated genomic profiling of endometrial carcinoma

ABSTRACT: Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation Although 75% of endometrial cancers are treated at an early stage, 15% to 20% of these recur. We performed an integrated analysis of genome-wide expression and copy-number data for primary endometrial carcinomas with extensive clinical and histopathological data to detect features predictive of recurrent disease. Unsupervised analysis of the expression data distinguished 2 major clusters with strikingly different phenotypes, including significant differences in disease-free survival. To identify possible mechanisms for these differences, we performed a global genomic survey of amplifications, deletions, and loss of heterozygosity, which identified 11 significantly amplified and 13 significantly deleted regions. Amplifications of 3q26.32 harboring the oncogene PIK3CA were associated with poor prognosis and segregated with the aggressive transcriptional cluster. Moreover, samples with PIK3CA amplification carried signatures associated with in vitro activation of PI3 kinase (PI3K), a signature that was shared by aggressive tumors without PIK3CA amplification. Tumors with loss of PTEN expression or PIK3CA overexpression that did not have PIK3CA amplification also shared the PI3K activation signature, high protein expression of the PI3K pathway member STMN1, and an aggressive phenotype in test and validation datasets. However, mutations of PTEN or PIK3CA were not associated with the same expression profile or aggressive phenotype. STMN1 expression had independent prognostic value. The results affirm the utility of systematic characterization of the cancer genome in clinically annotated specimens and suggest the particular importance of the PI3K pathway in patients who have aggressive endometrial cancer. 84 endometrial cancers (including 9 cell lines) were subject to 100K SNP analysis. 57 endometrial cancers were subject to expression analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Helga Salvesen 

PROVIDER: E-GEOD-14860 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

Json Xml
altmetric image

Publications

Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation.

Salvesen H B HB   Carter S L SL   Mannelqvist M M   Dutt A A   Getz G G   Stefansson I M IM   Raeder M B MB   Sos M L ML   Engelsen I B IB   Trovik J J   Wik E E   Greulich H H   Bø T H TH   Jonassen I I   Thomas R K RK   Zander T T   Garraway L A LA   Oyan A M AM   Sellers W R WR   Kalland K H KH   Meyerson M M   Akslen L A LA   Beroukhim R R  

Proceedings of the National Academy of Sciences of the United States of America 20090304 12

Although 75% of endometrial cancers are treated at an early stage, 15% to 20% of these recur. We performed an integrated analysis of genome-wide expression and copy-number data for primary endometrial carcinomas with extensive clinical and histopathological data to detect features predictive of recurrent disease. Unsupervised analysis of the expression data distinguished 2 major clusters with strikingly different phenotypes, including significant differences in disease-free survival. To identify  ...[more]

Similar Datasets

Genomics Integrated genomic profiling of endometrial carcinoma
2009-03-24 | GSE14860 | GEO
Transcriptomics Affymetrix SNP array data for mammary tumors that recurred after inactivation of the oncogenic PIK3CA-H1047R
2011-08-01 | E-GEOD-27691 | biostudies-arrayexpress
Proteomics High-dose oncogenic PIK3CA drives constitutive cellular stemness through increased NODAL/TGFb signaling
2021-03-03 | PXD014719 | Pride
Transcriptomics Mutant PI3K cooperates with HER2 to promote mammary tumor formation and induces trastuzumab resistance in vivo
2013-09-03 | E-GEOD-41118 | biostudies-arrayexpress
Transcriptomics Copy number profiling of 92 human lung tumors on Affymetrix 100K SNP arrays
2013-01-10 | E-GEOD-39793 | biostudies-arrayexpress
Transcriptomics Conditional loss of ErbB3 delays mammary gland hyperplasias induced by mutant PIK3CA but does not affect mammary tumor latency, gene expression or signaling
2013-06-20 | E-GEOD-43037 | biostudies-arrayexpress
Transcriptomics ARID1A and PI3-Kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion [12Z_1A_PI3K_RNA-seq]
2019-07-01 | GSE129779 | GEO
Transcriptomics ARID1A and PI3-Kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion [Mouse_RNA-seq]
2019-07-01 | GSE129784 | GEO
Genomics ARID1A and PI3-Kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion [Mouse_ATAC-seq]
2019-07-01 | GSE129783 | GEO
Transcriptomics ARID1A and PI3-Kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion [12Z_RNA-seq]
2019-07-01 | GSE129782 | GEO