Reduced rate of copy number aberrations in mucinous colorectal carcinoma.
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.
Department of Surgery, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
Niek
N
Hugen
Department of Pathology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
Femke
F
Simmer
Department of Internal Medicine, Medical Spectrum Twente Enschede, 7500 KA Enschede, The Netherlands.
Leonie J M
LJ
Mekenkamp
Department of Medical Oncology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
Miriam
M
Koopman
Department of Pathology, VU University Medical Centre, 1007 MB Amsterdam, The Netherlands.
Evert
E
van den Broek
Department of Surgery, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
Johannes H W
JH
de Wilt
Department of Medical Oncology, Academic Medical Center University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
Cornelis J A
CJ
Punt
Department of Pathology, VU University Medical Centre, 1007 MB Amsterdam, The Netherlands.
Bauke
B
Ylstra
Department of Pathology, VU University Medical Centre, 1007 MB Amsterdam, The Netherlands.
Gerrit A
GA
Meijer
Department of Pathology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
Iris D
ID
Nagtegaal
D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D014408:Biomarkers, Tumor / Q000235:genetics*; D043171:Chromosomal Instability; D002887:Chromosomes, Human, Pair 18; D002890:Chromosomes, Human, Pair 20; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D010641:Phenotype; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013997:Time Factors
D014408:Biomarkers, Tumor
colorectal adenocarcinoma; comparative genomic hybridization; copy number profile; mucinous carcinoma