Robust genomic copy number predictor of pan cancer metastasis

Alexander Pearlman, Kinnari Upadhyay, Kim Cole, Johnny C. Loke, Katherine Sun, Susan A. Fineberg, Stephen J. Freedland, Yongzhao Shao, Harry Ostrer

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Copy number alterations(CNAs) are the most common genetic changes observed in many cancers, reflecting the innate chromosomal instability of this disorder. Yet, how these alterations affect gene function to promote metastases across different tumor types has not been established. In this study, we developed a pan-cancer metastasis potential score (panMPS) based on observed CNAs. panMPS predicts metastasis and metastasis-free survival in cohorts of patients with prostate cancer, triple negative breast cancer and lung adenocarcinoma, and overall survival in the Metabric breast cancer cohort and three cohorts from The Cancer Genome Atlas (TCGA), including prostate, breast and lung adenocarcinoma. These CNAs are present in cell lines of metastatic tumors from eight different origins, reflected by an elevated panMPS for all cell lines. Many copy number alterations involve large chromosomal segments that encompass multiple genes (“clumps”). We show that harnessing this structural information to select only one gene per clump captures the contributions of other genes within the clump, resulting in a robust predictor of metastasis outcome. These sets of selected genes are distinct from cancer drivers that undergo mutation, and in fact, metastasis-related functions have been published for over half of them.

Original languageEnglish (US)
Pages (from-to)873-884
Number of pages12
JournalGenes and Cancer
Volume9
Issue number1-2
DOIs
StatePublished - Jan 1 2018

Fingerprint

Neoplasm Metastasis
Neoplasms
Genes
Chromosome Disorders
Triple Negative Breast Neoplasms
Chromosomal Instability
Survival
Atlases
Neoplasm Genes
Tumor Cell Line
Prostate
Lung Neoplasms
Prostatic Neoplasms
Breast
Genome
Breast Neoplasms
Cell Line
Mutation
Adenocarcinoma of lung

Keywords

  • Cancer
  • Genomic
  • Metastasis

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Robust genomic copy number predictor of pan cancer metastasis. / Pearlman, Alexander; Upadhyay, Kinnari; Cole, Kim; Loke, Johnny C.; Sun, Katherine; Fineberg, Susan A.; Freedland, Stephen J.; Shao, Yongzhao; Ostrer, Harry.

In: Genes and Cancer, Vol. 9, No. 1-2, 01.01.2018, p. 873-884.

Research output: Contribution to journalArticle

Pearlman, A, Upadhyay, K, Cole, K, Loke, JC, Sun, K, Fineberg, SA, Freedland, SJ, Shao, Y & Ostrer, H 2018, 'Robust genomic copy number predictor of pan cancer metastasis', Genes and Cancer, vol. 9, no. 1-2, pp. 873-884. https://doi.org/10.18632/genesandcancer.165
Pearlman A, Upadhyay K, Cole K, Loke JC, Sun K, Fineberg SA et al. Robust genomic copy number predictor of pan cancer metastasis. Genes and Cancer. 2018 Jan 1;9(1-2):873-884. https://doi.org/10.18632/genesandcancer.165
Pearlman, Alexander ; Upadhyay, Kinnari ; Cole, Kim ; Loke, Johnny C. ; Sun, Katherine ; Fineberg, Susan A. ; Freedland, Stephen J. ; Shao, Yongzhao ; Ostrer, Harry. / Robust genomic copy number predictor of pan cancer metastasis. In: Genes and Cancer. 2018 ; Vol. 9, No. 1-2. pp. 873-884.
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