Faculty Opinions recommendation of GPCRs show widespread differential mRNA expression and frequent mutation and copy number variation in solid tumors.

AbstractG protein-coupled receptors (GPCRs) are the most widely targeted gene family for FDA-approved drugs. To assess possible roles for GPCRs in cancer, we analyzed Cancer Genome Atlas data for mRNA expression, mutations, and copy number variation (CNV) in 20 categories/45 sub-types of solid tumors and quantified differential expression of GPCRs by comparing tumors against normal tissue from the GTEx database. GPCRs are over-represented among coding genes with elevated expression in solid tumors; most tumor types differentially express >50 GPCRs, including many targets for approved drugs, hitherto largely unrecognized as targets of interest in cancer. GPCR mRNA signatures characterize specific tumor types, indicate survival and correlate with expression of cancer-related pathways. Tumor GPCR mRNA signatures have prognostic relevance for survival and correlate with expression of numerous cancer-related genes and pathways. GPCR expression in tumors is largely independent of staging/grading/metastasis/driver mutations and GPCRs expressed in cancer cell lines parallels that measured in tumors. Certain GPCRs are frequently mutated and appear to be hotspots, serving as bellwethers of accumulated genomic damage. CNV of GPCRs while common, does not generally correlate with mRNA expression. We suggest a previously under-appreciated role for GPCRs in cancer, perhaps as functional oncogenes, biomarkers, surface antigens and pharmacological targets.

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Abstract B187: Prevalence of MET copy number variation, MET expression and MET related genomic alterations in all solid tumors pre-screening program. VHIO experience

10.1158/1535-7163.targ-15-b187 ◽

2015 ◽

Author(s):

Analía Azaro ◽

Guillem Argilés ◽

María Alsina ◽

Elena Elez ◽

Teresa Macarulla ◽

...

Keyword(s):

Copy Number Variation ◽

Solid Tumors ◽

Copy Number ◽

Screening Program ◽

Genomic Alterations ◽

Number Variation

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Copy Number Variation in Triple Negative Breast Cancer Samples Associated with Lymph Node Metastasis

10.21203/rs.3.rs-54764/v1 ◽

2020 ◽

Author(s):

Mamta Pariyar ◽

Andrea Johns ◽

Rick Francis Thorne ◽

Rodney J. Scott ◽

Kelly A. Avery-Kiejda

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Copy Number Variation ◽

Mrna Expression ◽

Triple Negative Breast Cancer ◽

Copy Number ◽

Triple Negative ◽

Node Metastasis ◽

Number Variation

Abstract BackgroundTriple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. MethodsCNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDC), 12 lymph node metastases (LNmets) and 7 normal adjacent tissues (NAT); as well as in a second cohort containing 70 TNBC IDC samples and the same 7 NATs. CNVs associated genes were analysed using GO-enrichment and Pathway analysis and also integrated with gene expression analysis. The prognostic role for genes showing CNV based change in mRNA expression was determined using Kaplan-Meier (KM) plotter database. ResultsFor the IDCs, frequent amplification was evident in chromosomal regions 8q, 1q, 2(p and q), 3q24, 10p and 12p and deletion in 3p, 4 (p and q), 5q, 14q and 17p in contrast to LNmets showing frequent amplification of 4q, 2p, 3q24, 1q, 10p, 12p, 8q, 20p, 21q and 6p and deletion in 1p, 4q (4q21.1, 4q26) and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with lymph node metastasis. The LNmet-associated genes were highly enriched for “regulation of complement activation”, “regulation of protein activation cascade”, “regulation of humoral immune response”, “oxytocin signalling pathway” and “trail binding” pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse free survival.ConclusionThis study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.

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