Oncotarget

Research Papers:

Reduced rate of copy number aberrations in mucinous colorectal carcinoma

Niek Hugen _, Femke Simmer, Leonie J.M. Mekenkamp, Miriam Koopman, Evert van den Broek, Johannes H.W. de Wilt, Cornelis J.A. Punt, Bauke Ylstra, Gerrit A. Meijer and Iris D. Nagtegaal

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Oncotarget. 2015; 6:25715-25725. https://doi.org/10.18632/oncotarget.4706

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Abstract

Niek Hugen1,*, Femke Simmer2,*, Leonie J.M. Mekenkamp3, Miriam Koopman4, Evert van den Broek5, Johannes H.W. de Wilt1, Cornelis J.A. Punt6, Bauke Ylstra5, Gerrit A. Meijer5,#, Iris D. Nagtegaal2,#

1Department of Surgery, Radboud university medical center, 6500 HB Nijmegen, The Netherlands

2Department of Pathology, Radboud university medical center, 6500 HB Nijmegen, The Netherlands

3Department of Internal Medicine, Medical Spectrum Twente Enschede, 7500 KA Enschede, The Netherlands

4Department of Medical Oncology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands

5Department of Pathology, VU University Medical Centre, 1007 MB Amsterdam, The Netherlands

6Department of Medical Oncology, Academic Medical Center University of Amsterdam, 1100 DD Amsterdam, The Netherlands

*These authors have contributed equally to this work

#These authors have contributed equally to this work

Correspondence to:

Niek Hugen, e-mail: [email protected]

Keywords: colorectal adenocarcinoma, mucinous carcinoma, comparative genomic hybridization, copy number profile

Received: April 23, 2015     Accepted: July 13, 2015     Published: July 25, 2015

ABSTRACT

Background: Mucinous carcinoma (MC) is found in 10%–15% of colorectal cancer (CRC) patients. It differs from the common adenocarcinoma (AC) in histopathological appearance and clinical behavior.

Methods: Genome-wide DNA copy number and survival data from MC and AC primary CRC samples from patients from two phase III trials (CAIRO and CAIRO2) was compared. Chromosomal copy number data from The Cancer Genome Atlas (TCGA) was used for validation. Altogether, 470 ACs were compared to 57 MCs.

Results: MC showed a reduced amount of copy number aberrations (CNAs) compared with AC for the CAIRO/CAIRO2 cohort, with a median amount of CNAs that was 1.5-fold lower (P = 0.002). Data from TCGA also showed a reduced amount of CNAs for MC. MC samples in both cohorts displayed less gain at chromosome 20q and less loss of chromosome 18p. A high rate of chromosomal instability was a strong negative prognostic marker for survival in MC patients from the CAIRO cohorts (hazard ratio 15.60, 95% CI 3.24–75.05).

Conclusions: Results from this study indicate that the distinct MC phenotype is accompanied by a different genetic basis when compared with AC and show a strong association between the rate of chromosomal instability and survival in MC patients.


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