Tampere University of Technology

TUTCRIS Research Portal

Clustering-based method for developing a genomic copy number alteration signature for predicting the metastatic potential of prostate cancer

Research output: Contribution to journalArticleScientificpeer-review

Details

Original languageEnglish
Article number873570
JournalJOURNAL OF PROBABILITY AND STATISTICS
DOIs
Publication statusPublished - 2012
Publication typeA1 Journal article-refereed

Abstract

The transition of cancer from a localized tumor to a distant metastasis is not well understood for prostate and many other cancers, partly, because of the scarcity of tumor samples, especially metastases, from cancer patients with long-term clinical follow-up. To overcome this limitation, we developed a semi-supervised clustering method using the tumor genomic DNA copy number alterations to classify each patient into inferred clinical outcome groups of metastatic potential. Our data set was comprised of 294 primary tumors and 49 metastases from 5 independent cohorts of prostate cancer patients. The alterations were modeled based on Darwins evolutionary selection theory and the genes overlapping these altered genomic regions were used to develop a metastatic potential score for a prostate cancer primary tumor. The function of the proteins encoded by some of the predictor genes promote escape from anoikis, a pathway of apoptosis, deregulated in metastases. We evaluated the metastatic potential score with other clinical predictors available at diagnosis using a Cox proportional hazards model and show our proposed score was the only significant predictor of metastasis free survival. The metastasis gene signature and associated score could be applied directly to copy number alteration profiles from patient biopsies positive for prostate cancer.

ASJC Scopus subject areas