Genomic and epigenetic aberrations of chromosome 1p36.13 have prognostic implications in malignancies
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ORIGINAL ARTICLE
Genomic and epigenetic aberrations of chromosome 1p36.13 have prognostic implications in malignancies Ali Naderi
Received: 29 June 2020 / Revised: 9 August 2020 / Accepted: 16 August 2020 # Springer Nature B.V. 2020
Abstract Deletions of chromosome 1p36 are common in malignancies; however, there is limited information regarding the biological and prognostic implications of 1p36 in cancer. Steroid Receptor–Associated and Regulated Protein (SRARP) is a tumor suppressor on chromosome 1p36.13 that its inactivation predicts poor cancer outcome, indicating that the 1p36.13 segment requires further studies. Therefore, a comprehensive multi-omics analysis of The Cancer Genome Atlas (TCGA), the Pan-Cancer Analysis of Whole Genomes (PCAWD), the International Cancer Genome Consortium (ICGC), and the Genomic Data Commons (GDC) Pan-Cancer datasets was conducted to investigate the prognostic implications of 1p36.13 in malignancies. This study revealed that expression and DNA methylation of multiple genes on 1p36.13 are significantly associated with survival in primary tumors and normal adjacent tissues. In addition, copy-number loss in every gene on 1p36.13 predicts poor cancer outcome. Importantly, copy-number loss and somatic mutations of chromosome 1p36.13 segment are associated with worse survival in primary tumors, and DNA hypermethylation of 1p36.13 predicts poor outcome in normal adjacent tissues. Therefore, genomic and
Responsible Editor: Matthew Breen
epigenetic aberrations of chromosome 1p36.13 have promising prognostic implications in cancer. Keywords 1p36.13 . cancer outcome . gene expression . copy-number . DNA methylation . mutation Abbreviations SRARP Steroid Receptor–Associated and Regulated Protein AR Androgen receptor Mb Megabases TCGA The Cancer Genome Atlas RNAseq RNA sequencing RSEM RNA Seq by Expectation Maximization PCAWG The Pan-Cancer Analysis of Whole Genomes GDC The Genomic Data Commons FPKM-UQ Fragments per kilobase of transcript per million mapped reads upper quartile ICGC International Cancer Genome Consortium CNV Copy-number variation FDR False discovery rate DNA-VAF DNA-variant allele frequency.
A. Naderi Cancer Biology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA A. Naderi (*) Queensland University of Technology, Gardens Point, Brisbane, Queensland 4001, Australia e-mail: [email protected]
Introduction Deletions of the distal short arm of chromosome 1 (1p) were first reported in neuroblastomas in 1977 and are
A. Naderi
present in a wide range of malignancies (Brodeur et al. 1977; Henrich et al. 2012). In particular, chromosome 1p36 is frequently deleted in human cancers, and 1p36.1 loss occurs in about 34% of tumors (Knuutila et al. 1999; Henrich et al. 2012). It has also been suggested that 1p36 deletion is a marker for tumor dissemination in microsatellite stable colon cancer (Mayrhofer et al. 2014). However, despite extensive studies, there has been limited success for identifying candidate tumor suppressors on chromoso
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