Functional & Integrative Genomics

, Volume 17, Issue 1, pp 85–96 | Cite as

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

  • Weixiang Chen
  • Jun Ding
  • Long Jiang
  • Zebing Liu
  • Xiaoyan ZhouEmail author
  • Daren Shi
Original Article


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.


Colorectal cancer Hereditary non-polyposis colorectal cancer Microsatellite stable Copy number Loss of heterozygosity 



The authors acknowledge the help of the staff at the Department of Pathology of the Fudan University Shanghai Cancer Center.

Compliance with ethical standards


This work was supported by the National Natural Science Foundation of China (no. 81302163), Shanghai Pudong New Area science and technology development fund, innovation fund (no. PKJ2013-Y08), and Excellent Academic Leaders of Shanghai Pudong New Area (No.PWRd2013-01).

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal ethical rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Fudan University Shanghai Cancer Center research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Weixiang Chen
    • 1
  • Jun Ding
    • 1
  • Long Jiang
    • 2
  • Zebing Liu
    • 3
  • Xiaoyan Zhou
    • 4
    Email author
  • Daren Shi
    • 4
  1. 1.Department of PathologyShanghai Gongli HospitalShanghaiChina
  2. 2.Department of PathologyNingxia Medical UniversityNingxiaChina
  3. 3.Department of PathologyShanghai Jiaotong University Renji HospitalShanghaiChina
  4. 4.Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina

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