MiRNA expression in colon polyps provides evidence for a Multihit model of colon cancer

Ann L Oberg, Amy J. French, Aaron L. Sarver, Subbaya Subramanian, Bruce W. Morlan, Shaun M. Riska, Pedro M. Borralho, Julie M Cunningham, Lisa Allyn Boardman, Liang Wang, Thomas Christopher Smyrk, Yan Asmann, Clifford J. Steer, Stephen N Thibodeau

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evaluated. In this study, we examined the global miRNA expression in 315 samples that included 52 normal colonic mucosa, 41 tubulovillous adenomas, 158 adenocarcinomas with proficient DNA mismatch repair (pMMR) selected for stage and age of onset, and 64 adenocarcinomas with defective DNA mismatch repair (dMMR) selected for sporadic (n = 53) and inherited colon cancer (n = 11). Sporadic dMMR tumors all had MLH1 inactivation due to promoter hypermethylation. Unsupervised PCA and cluster analysis demonstrated that normal colon tissue, adenomas, pMMR carcinomas and dMMR carcinomas were all clearly discernable. The majority of miRNAs that were differentially expressed between normal and polyp were also differentially expressed with a similar magnitude in the comparison of normal to both the pMMR and dMMR tumor groups, suggesting a stepwise progression for transformation from normal colon to carcinoma. Among the miRNAs demonstrating the largest fold up- or down-regulated changes (≥4), four novel (miR-31, miR-1, miR-9 and miR-99a) and two previously reported (miR-137 and miR-135b) miRNAs were identified in the normal/adenoma comparison. All but one of these (miR-99a) demonstrated similar expression differences in the two normal/carcinoma comparisons, suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers. The comparison between pMMR and dMMR tumors identified four miRNAs (miR-31, miR-552, miR-592 and miR-224) with statistically significant expression differences (≥2-fold change).

Original languageEnglish (US)
Article numbere20465
JournalPLoS One
Volume6
Issue number6
DOIs
StatePublished - 2011

Fingerprint

DNA Mismatch Repair
Polyps
colorectal neoplasms
Colonic Neoplasms
colon
Colon
Repair
MicroRNAs
DNA
adenoma
Adenoma
carcinoma
Tumors
neoplasms
Carcinoma
microRNA
Neoplasms
adenocarcinoma
Adenocarcinoma
Passive Cutaneous Anaphylaxis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

MiRNA expression in colon polyps provides evidence for a Multihit model of colon cancer. / Oberg, Ann L; French, Amy J.; Sarver, Aaron L.; Subramanian, Subbaya; Morlan, Bruce W.; Riska, Shaun M.; Borralho, Pedro M.; Cunningham, Julie M; Boardman, Lisa Allyn; Wang, Liang; Smyrk, Thomas Christopher; Asmann, Yan; Steer, Clifford J.; Thibodeau, Stephen N.

In: PLoS One, Vol. 6, No. 6, e20465, 2011.

Research output: Contribution to journalArticle

Oberg, AL, French, AJ, Sarver, AL, Subramanian, S, Morlan, BW, Riska, SM, Borralho, PM, Cunningham, JM, Boardman, LA, Wang, L, Smyrk, TC, Asmann, Y, Steer, CJ & Thibodeau, SN 2011, 'MiRNA expression in colon polyps provides evidence for a Multihit model of colon cancer', PLoS One, vol. 6, no. 6, e20465. https://doi.org/10.1371/journal.pone.0020465
Oberg, Ann L ; French, Amy J. ; Sarver, Aaron L. ; Subramanian, Subbaya ; Morlan, Bruce W. ; Riska, Shaun M. ; Borralho, Pedro M. ; Cunningham, Julie M ; Boardman, Lisa Allyn ; Wang, Liang ; Smyrk, Thomas Christopher ; Asmann, Yan ; Steer, Clifford J. ; Thibodeau, Stephen N. / MiRNA expression in colon polyps provides evidence for a Multihit model of colon cancer. In: PLoS One. 2011 ; Vol. 6, No. 6.
@article{90c349da3d8f4627aef4f5b0b092a362,
title = "MiRNA expression in colon polyps provides evidence for a Multihit model of colon cancer",
abstract = "Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evaluated. In this study, we examined the global miRNA expression in 315 samples that included 52 normal colonic mucosa, 41 tubulovillous adenomas, 158 adenocarcinomas with proficient DNA mismatch repair (pMMR) selected for stage and age of onset, and 64 adenocarcinomas with defective DNA mismatch repair (dMMR) selected for sporadic (n = 53) and inherited colon cancer (n = 11). Sporadic dMMR tumors all had MLH1 inactivation due to promoter hypermethylation. Unsupervised PCA and cluster analysis demonstrated that normal colon tissue, adenomas, pMMR carcinomas and dMMR carcinomas were all clearly discernable. The majority of miRNAs that were differentially expressed between normal and polyp were also differentially expressed with a similar magnitude in the comparison of normal to both the pMMR and dMMR tumor groups, suggesting a stepwise progression for transformation from normal colon to carcinoma. Among the miRNAs demonstrating the largest fold up- or down-regulated changes (≥4), four novel (miR-31, miR-1, miR-9 and miR-99a) and two previously reported (miR-137 and miR-135b) miRNAs were identified in the normal/adenoma comparison. All but one of these (miR-99a) demonstrated similar expression differences in the two normal/carcinoma comparisons, suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers. The comparison between pMMR and dMMR tumors identified four miRNAs (miR-31, miR-552, miR-592 and miR-224) with statistically significant expression differences (≥2-fold change).",
author = "Oberg, {Ann L} and French, {Amy J.} and Sarver, {Aaron L.} and Subbaya Subramanian and Morlan, {Bruce W.} and Riska, {Shaun M.} and Borralho, {Pedro M.} and Cunningham, {Julie M} and Boardman, {Lisa Allyn} and Liang Wang and Smyrk, {Thomas Christopher} and Yan Asmann and Steer, {Clifford J.} and Thibodeau, {Stephen N}",
year = "2011",
doi = "10.1371/journal.pone.0020465",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - MiRNA expression in colon polyps provides evidence for a Multihit model of colon cancer

AU - Oberg, Ann L

AU - French, Amy J.

AU - Sarver, Aaron L.

AU - Subramanian, Subbaya

AU - Morlan, Bruce W.

AU - Riska, Shaun M.

AU - Borralho, Pedro M.

AU - Cunningham, Julie M

AU - Boardman, Lisa Allyn

AU - Wang, Liang

AU - Smyrk, Thomas Christopher

AU - Asmann, Yan

AU - Steer, Clifford J.

AU - Thibodeau, Stephen N

PY - 2011

Y1 - 2011

N2 - Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evaluated. In this study, we examined the global miRNA expression in 315 samples that included 52 normal colonic mucosa, 41 tubulovillous adenomas, 158 adenocarcinomas with proficient DNA mismatch repair (pMMR) selected for stage and age of onset, and 64 adenocarcinomas with defective DNA mismatch repair (dMMR) selected for sporadic (n = 53) and inherited colon cancer (n = 11). Sporadic dMMR tumors all had MLH1 inactivation due to promoter hypermethylation. Unsupervised PCA and cluster analysis demonstrated that normal colon tissue, adenomas, pMMR carcinomas and dMMR carcinomas were all clearly discernable. The majority of miRNAs that were differentially expressed between normal and polyp were also differentially expressed with a similar magnitude in the comparison of normal to both the pMMR and dMMR tumor groups, suggesting a stepwise progression for transformation from normal colon to carcinoma. Among the miRNAs demonstrating the largest fold up- or down-regulated changes (≥4), four novel (miR-31, miR-1, miR-9 and miR-99a) and two previously reported (miR-137 and miR-135b) miRNAs were identified in the normal/adenoma comparison. All but one of these (miR-99a) demonstrated similar expression differences in the two normal/carcinoma comparisons, suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers. The comparison between pMMR and dMMR tumors identified four miRNAs (miR-31, miR-552, miR-592 and miR-224) with statistically significant expression differences (≥2-fold change).

AB - Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evaluated. In this study, we examined the global miRNA expression in 315 samples that included 52 normal colonic mucosa, 41 tubulovillous adenomas, 158 adenocarcinomas with proficient DNA mismatch repair (pMMR) selected for stage and age of onset, and 64 adenocarcinomas with defective DNA mismatch repair (dMMR) selected for sporadic (n = 53) and inherited colon cancer (n = 11). Sporadic dMMR tumors all had MLH1 inactivation due to promoter hypermethylation. Unsupervised PCA and cluster analysis demonstrated that normal colon tissue, adenomas, pMMR carcinomas and dMMR carcinomas were all clearly discernable. The majority of miRNAs that were differentially expressed between normal and polyp were also differentially expressed with a similar magnitude in the comparison of normal to both the pMMR and dMMR tumor groups, suggesting a stepwise progression for transformation from normal colon to carcinoma. Among the miRNAs demonstrating the largest fold up- or down-regulated changes (≥4), four novel (miR-31, miR-1, miR-9 and miR-99a) and two previously reported (miR-137 and miR-135b) miRNAs were identified in the normal/adenoma comparison. All but one of these (miR-99a) demonstrated similar expression differences in the two normal/carcinoma comparisons, suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers. The comparison between pMMR and dMMR tumors identified four miRNAs (miR-31, miR-552, miR-592 and miR-224) with statistically significant expression differences (≥2-fold change).

UR - http://www.scopus.com/inward/record.url?scp=79958270237&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958270237&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0020465

DO - 10.1371/journal.pone.0020465

M3 - Article

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e20465

ER -