Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human high-grade astrocytomas reveals prognostic subgroups

ABSTRACT: Novel prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit either markers of proliferation or of angiogenesis and mesenchyme. Analysis of gene expression data is described in Phillips et al., Cancer Cell, 2006. Experiment Overall Design: 77 primary high-grade astrocytomas and 23 matched recurrences were profiled to identify changes in gene expression that relate to both survival and disease progression. Samples include WHO grade III and IV astrocytomas with a wide range of survival times.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens

SUBMITTER: Thomas Wu

PROVIDER: E-GEOD-4271 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.

Phillips Heidi S HS Kharbanda Samir S Chen Ruihuan R Forrest William F WF Soriano Robert H RH Wu Thomas D TD Misra Anjan A Nigro Janice M JM Colman Howard H Soroceanu Liliana L Williams P Mickey PM Modrusan Zora Z Feuerstein Burt G BG Aldape Ken K

Cancer cell 20060301 3

Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit markers either of proliferation or of angiogenesis and mesenchyme. Upon recurrence, tumors frequently shift toward the mesenchymal subclass. Chromosomal locatio ...[more]

PMID: 16530701

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Project description:Histological grading of breast cancer defines morphological subtypes informative of metastatic potential, although not without considerable inter-observer disagreement and clinical heterogeneity particularly among the moderately differentiated grade II (G2) tumors. We posited that a gene expression signature capable of discerning tumors of grade I (G1) and grade III (G3) histology might provide a more objective measure of grade with prognostic benefit for patients with moderately differentiated disease. To this end, we studied the expression profiles of 347 primary invasive breast tumors analyzed on Affymetrix microarrays. Using class prediction algorithms, we identified 264 robust grade-associated markers, six of which could accurately classify G1 and G3 tumors, and separate G2 tumors into two highly discriminant classes (termed G2a and G2b genetic grades) with patient survival outcomes highly similar to those with G1 and G3 histology, respectively. Statistical analysis of conventional clinical variables further distinguished G2a and G2b subtypes from each other, but also from histologic G1 and G3 tumors. In multivariate analyses, genetic grade was consistently found to be an independent prognostic indicator of disease recurrence comparable to that of lymph node status and tumor size. When incorporated into the Nottingham Prognostic Index, genetic grade enhanced detection of patients with less harmful tumors, likely to benefit little from adjuvant therapy. Our findings show that a genetic grade signature can improve prognosis and therapeutic planning for breast cancer patients, and support the view that low and high grade disease, as defined genetically, reflect independent pathobiological entities rather than a continuum of cancer progression. Three separate breast cancer cohorts were analyzed: 1) Uppsala (n=249), 2) Stockholm (n=58), 3) Singapore (n=40). The Uppsala and Singapore data can be accessed here. The Stockholm cohort data can be accessed at GEO Series GSE1456. Experiment Overall Design: All tumor specimens were assessed on U133 A and B arrays.

Dataset Information

Transcription profiling of human high-grade astrocytomas reveals prognostic subgroups

Publications

Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.

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