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Patterns of somatic uniparental disomy identify driver tumor suppressor genes in colorectal cancer [Illumina]


ABSTRACT: The aim of this study is to establish an integrative profiling of recurrent UPDs/UPPs, CNAs and genome-wide methylation status in sporadic CRC. Our results indicate that regions showing high frequencies of UPDs/UPPs mostly coincide with regions typically involved in genomic losses such as chromosome arms 1p, 5q, 8p, 14q, 17p, 18q, 20p, and 22q. Of these, chromosome arms 5q, 14q, 17p, and 20p preferentially showed UPDs/UPPs over genomic losses suggesting that tumor cells must maintain the disomic state of certain genes to favor cellular fitness. A meta-analysis using over 300 samples from The Cancer Genome Atlas confirmed our findings. In addition, the genes CSPG2, FLT4, SFRP1, DLK1, and GAS7 were frequently involved in regions of UPDs/UPPs and showed high levels of methylation revealing that UPDs/UPPs can result in the duplication of hypermethylated inactive genes. A total of 32 primary tumors from the colon and rectum were collected from the Hospital Clinic of Barcelona under the supervision of an experienced pathologist. DNA was extracted and bisulfited according to manufacturer's protocols. Matched patient DNA from normal mucosa was used as a reference for these experiments. This dataset includes methylation data for 29 colorectal cancers (only including those with good QC).

ORGANISM(S): Homo sapiens

SUBMITTER: Jordi Camps 

PROVIDER: E-GEOD-64112 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Colorectal cancer (CRC) is characterized by specific patterns of copy number alterations (CNAs), which helped with the identification of driver oncogenes and tumor suppressor genes (TSGs). More recently, the usage of single nucleotide polymorphism arrays provided information of copy number neutral loss of heterozygosity, thus suggesting the occurrence of somatic uniparental disomy (UPD) and uniparental polysomy (UPP) events. The aim of this study is to establish an integrative profiling of recur  ...[more]

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