We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Papillary renal cell carcinoma: More than one entity based on molecular subtyping and pathway analysis.
- Authors
Saleeb, Rola M.; Plant, Pamela; Tawedrous, Eriny; Krizova, Adriana; Al-Haddad, Sahar; Evans, Andrew J.; Brimo, Fady; Wala, Samantha; Qiang Ding; Yousef, George M.
- Abstract
Objective: Papillary Renal Cell Carcinoma (PRCC) is recognized to have two histologic subtypes. Previous studies have shown the subtypes have different characteristic genetic alterations, and clinical behavior. We aimed to elucidate the molecular differences between the subtypes on the genetic, and epigenetic level and to gain insight into the molecular pathways that drive tumour behavior. Methods: Patient cohort PRCC, 291, of the Cancer Atlas Genome (TCGA) was divided on histologic criteria into type 1, type 2 or not-otherwise specified (NOS). Gene expression (RNA seq) data for the cohort was examined using unsupervised clustering, and supervised clustering bioinformatics analysis. A total of 35 primary PRCC specimens were also collected, for miRNA analysis, after similar histologic subclassification. Gene set enrichment analysis (GSEA) was performed on both cohorts. Data and Results: Analysis of gene expression and miRNA expression between the subtypes using unsupervised clustering revealed two distinct genetic tumour signatures. Supervised clustering produced statistically significant identifying markers for each subtype. GSEA revealed considerably different pathways implicated in each type including VEGF, mTOR, and Wnt signaling pathways. Conclusions: Investigating the subtypes of PRCC at the molecular level, revealed that each have distinct genetic signatures and implied molecular pathways. Our findings highlight the need to segregate between the types in clinical assessment and management; given that the subtypes may have differing responses to current targeted molecular therapies. There is also a need to identify robust markers for pathologists to aid in the distinction between the subtypes, and to accurately classify tumours within the PRCC NOS category.
- Publication
Canadian Journal of Pathology, 2016, Vol 8, p36
- ISSN
1918-915X
- Publication type
Article