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Table S1, S2, S3 from Genetic and Epigenetic Determinants of Aggressiveness in Cribriform Carcinoma of the Prostate

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posted on 2023-04-03, 17:28 authored by Habiba Elfandy, Joshua Armenia, Filippo Pederzoli, Eli Pullman, Nelma Pertega-Gomes, Nikolaus Schultz, Kartik Viswanathan, Aram Vosoughi, Mirjam Blattner, Konrad H. Stopsack, Giorgia Zadra, Kathryn L. Penney, Juan Miguel Mosquera, Svitlana Tyekucheva, Lorelei A. Mucci, Christopher Barbieri, Massimo Loda

Table S1: IDs of Cribriform (ICC) & Non-cribriform (NC4) TCGA cases; Table S2: Comparison between cribriform and non-cribriform based on TCGA clusters; Table S3: Somatic Copy Number Variation (SCNV) enriched in Cribriform Carcinoma (ICC) compared to Noncribriform (NC4), corrected for Fraction Genome Altered (FGA) and Gleason Score (GS).

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ARTICLE ABSTRACT

Among prostate cancers containing Gleason pattern 4, cribriform morphology is associated with unfavorable clinicopathologic factors, but its genetic features and association with long-term outcomes are incompletely understood. In this study, genetic, transcriptional, and epigenetic features of invasive cribriform carcinoma (ICC) tumors were compared with non-cribriform Gleason 4 (NC4) in The Cancer Genome Atlas (TCGA) cohort. ICC (n = 164) had distinctive molecular features when compared with NC4 (n = 102). These include: (i) increased somatic copy number variations (SCNV), specifically deletions at 6q, 8p and 10q, which encompassed PTEN and MAP3K7 losses and gains at 3q; (ii) increased SPOPmut and ATMmut; (iii) enrichment for mTORC1 and MYC pathways by gene expression; and (iv) increased methylation of selected genes. In addition, when compared with the metastatic prostate cancer, ICC clustered more closely to metastatic prostate cancer than NC4. Validation in clinical cohorts and genomically annotated murine models confirmed the association with SPOPmut (n = 38) and PTENloss (n = 818). The association of ICC with lethal disease was evaluated in the Health Professionals Follow-up Study (HPFS) and Physicians' Health Study (PHS) prospective prostate cancer cohorts (median follow-up, 13.4 years; n = 818). Patients with ICC were more likely to develop lethal cancer [HR, 1.62; 95% confidence interval (CI), 1.05–2.49], independent from Gleason score (GS). ICC has a distinct molecular phenotype that resembles metastatic prostate cancer and is associated with progression to lethal disease.

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