DNA copy number profiling in microsatellite-stable and microsatellite-unstable hereditary non-polyposis colorectal cancers by targeted CNV array View Full Text


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Article Info

DATE

2016-11-28

AUTHORS

Weixiang Chen, Jun Ding, Long Jiang, Zebing Liu, Xiaoyan Zhou, Daren Shi

ABSTRACT

About half of hereditary non-polyposis colorectal cancers (HNPCCs) fulfilling the Amsterdam criteria (AC) do not display evidence of mismatch repair defects, and the difference between microsatellite-stable (MSS) and microsatellite-unstable HNPCC remains poorly understood. The study was to compare overall copy number variation (CNV) and loss of heterozygosity (LOH) of the entire genome in HNPCCs with MSS and microsatellite-instability (MSI) using the Cytoscan HD Array. This was a study carried out in samples from 20 patients with MSS HNPCC and four patients with MSI HNPCC from the Fudan University Shanghai Cancer Center (China). The microsatellite status was examined using a panel of microsatellite markers. MMR expression status was evaluated by immunohistochemistry. Tumor samples were analyzed with the Genome-Wide Human CytoScan HD Array. CNV and LOH were determined. Fourteen specific CNVs (eight gains: 5p13.1, 7p13, 7q22.3, 8q11.21, 8q12.2, 19q13.11, 20q11.21, and 20q11.23; and six losses: 8p22, 8p23.1, 8p23.1, 17p13.1, 17p13.2, and 18q21.3) were associated with MSS HNPCC. Of these 14 CNVs, gain on 8q12.2 and loss on 17p13.1 were novel. The total length of 8q gains and 20q gains were greater in MSS tumors than in MSI (P < 0.05). The presence of similar levels of copy-neutral-LOH in MSS (31.7%) and MSI (29.7%) HNPCC suggested that unknown DNA repair genes might be involved in the tumorigenesis of MSS HNPCC. MSS HNPCC is a genetically specific population with increased CNV, which are different from MSI HNPCC. The results may help to clarify the genetic basis of MSS HNPCC tumorigenesis. More... »

PAGES

85-96

References to SciGraph publications

  • 2008-04-15. Genome-wide copy neutral LOH is infrequent in familial and sporadic microsatellite unstable carcinomas in FAMILIAL CANCER
  • 2009-03-08. The impact of copy number variation on local gene expression in mouse hematopoietic stem/progenitor cells in NATURE GENETICS
  • 2015-06-24. Epigenetics could explain some Moroccan population colorectal cancers peculiarities: microsatellite instability pathway exploration in DIAGNOSTIC PATHOLOGY
  • 2014-12-11. A high-resolution copy-number variation resource for clinical and population genetics in GENETICS IN MEDICINE
  • 2009-10. Finding the missing heritability of complex diseases in NATURE
  • 2005-01-17. Comprehensive characterization of HNPCC-related colorectal cancers reveals striking molecular features in families with no germline mismatch repair gene mutations in ONCOGENE
  • 2013-05-26. Copy number variation-based polymorphism in a new pseudoautosomal region 3 (PAR3) of a human X-chromosome-transposed region (XTR) in the Y chromosome in FUNCTIONAL & INTEGRATIVE GENOMICS
  • 2011-08-23. Mechanism of action of vitamin D and the vitamin D receptor in colorectal cancer prevention and treatment in REVIEWS IN ENDOCRINE AND METABOLIC DISORDERS
  • 2011-01-04. Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose–response meta-analysis in CANCER CAUSES & CONTROL
  • 2012-07-13. Copy number variation in the cattle genome in FUNCTIONAL & INTEGRATIVE GENOMICS
  • 2004-08-01. Detection of large-scale variation in the human genome in NATURE GENETICS
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    http://scigraph.springernature.com/pub.10.1007/s10142-016-0532-x

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    http://dx.doi.org/10.1007/s10142-016-0532-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1051821348

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27896456


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