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; Iris D Nagtegaal

doi:10.18632/oncotarget.4706

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, Iris D Nagtegaal

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	25715-25725
Number of pages	11
Journal	Oncotarget
Volume	6
Issue number	28
DOIs	https://doi.org/10.18632/oncotarget.4706
Publication status	Published - 22 Sept 2015

Keywords

Adenocarcinoma, Mucinous
Biomarkers, Tumor
Chromosomal Instability
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 20
Clinical Trials, Phase III as Topic
Colorectal Neoplasms
DNA Copy Number Variations
Databases, Genetic
Gene Dosage
Genetic Predisposition to Disease
Humans
Kaplan-Meier Estimate
Phenotype
Proportional Hazards Models
Randomized Controlled Trials as Topic
Risk Factors
Time Factors
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Access to Document

10.18632/oncotarget.4706

4706-67921-2-PBFinal published version, 3.18 MB

Cite this

@article{dc43358ab5f547d3bdef38bdd3219f37,

title = "Reduced rate of copy number aberrations in mucinous colorectal carcinoma",

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.",

keywords = "Adenocarcinoma, Mucinous, Biomarkers, Tumor, Chromosomal Instability, Chromosomes, Human, Pair 18, Chromosomes, Human, Pair 20, Clinical Trials, Phase III as Topic, Colorectal Neoplasms, DNA Copy Number Variations, Databases, Genetic, Gene Dosage, Genetic Predisposition to Disease, Humans, Kaplan-Meier Estimate, Phenotype, Proportional Hazards Models, Randomized Controlled Trials as Topic, Risk Factors, Time Factors, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't",

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

year = "2015",

month = sep,

day = "22",

doi = "10.18632/oncotarget.4706",

language = "English",

volume = "6",

pages = "25715--25725",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals",

number = "28",

}

TY - JOUR

T1 - Reduced rate of copy number aberrations in mucinous colorectal carcinoma

AU - Hugen, Niek

AU - Simmer, Femke

AU - Mekenkamp, Leonie J M

AU - Koopman, Miriam

AU - van den Broek, Evert

AU - de Wilt, Johannes H W

AU - Punt, Cornelis J A

AU - Ylstra, Bauke

AU - Meijer, Gerrit A

AU - Nagtegaal, Iris D

PY - 2015/9/22

Y1 - 2015/9/22

N2 - 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.

AB - 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.

KW - Adenocarcinoma, Mucinous

KW - Biomarkers, Tumor

KW - Chromosomal Instability

KW - Chromosomes, Human, Pair 18

KW - Chromosomes, Human, Pair 20

KW - Clinical Trials, Phase III as Topic

KW - Colorectal Neoplasms

KW - DNA Copy Number Variations

KW - Databases, Genetic

KW - Gene Dosage

KW - Genetic Predisposition to Disease

KW - Humans

KW - Kaplan-Meier Estimate

KW - Phenotype

KW - Proportional Hazards Models

KW - Randomized Controlled Trials as Topic

KW - Risk Factors

KW - Time Factors

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.18632/oncotarget.4706

DO - 10.18632/oncotarget.4706

M3 - Article

C2 - 26329972

SN - 1949-2553

VL - 6

SP - 25715

EP - 25725

JO - Oncotarget

JF - Oncotarget

IS - 28

ER -

Reduced rate of copy number aberrations in mucinous colorectal carcinoma

Abstract

Keywords

Access to Document

Fingerprint

Cite this