Prognostic Impact of Deficient DNA Mismatch Repair and KRAS and BRAFV600E Mutations in Patients with Lymph-Node-Positive Colon Cancer

Aziz Zaanan, Jean Baptiste Bachet, Thierry André, Frank A Sinicrope

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Although tumor stage remains the key determinant of colorectal cancer prognosis and treatment, there is considerable stage-independent variability in clinical outcome. Molecular markers hold promise for explaining variations in clinical behavior, and may identify patient subsets with differential efficacy and survival after adjuvant chemotherapy, which is the standard of care for patients with lymph-node-positive, i.e., stage III, colon cancer. An increased understanding of the molecular evolution and progression of colorectal cancer has identified two major pathways of tumorigenesis that are characterized by chromosomal instability and by microsatellite instability. Microsatellite instability is a consequence of deficient DNA mismatch repair that is generally due to epigenetic inactivation of MLH1 in tumors that often carry mutations (V600E) in oncogenic BRAF. Activating BRAFV600E and KRAS mutations are mutually exclusive, and in this article, we review the current status of these mutations and the mismatch repair status as prognostic biomarkers in stage III colon cancers.

Original languageEnglish (US)
JournalCurrent Colorectal Cancer Reports
DOIs
StateAccepted/In press - Jun 29 2014

Fingerprint

DNA Repair-Deficiency Disorders
DNA Mismatch Repair
Colonic Neoplasms
Microsatellite Instability
Lymph Nodes
Mutation
Colorectal Neoplasms
Chromosomal Instability
Molecular Evolution
Adjuvant Chemotherapy
Standard of Care
Epigenomics
Neoplasms
Carcinogenesis
Biomarkers
Survival
Therapeutics

Keywords

  • Biomarker
  • BRAF
  • Colorectal cancer
  • KRAS
  • Microsatellite instability
  • Prognosis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Oncology

Cite this

Prognostic Impact of Deficient DNA Mismatch Repair and KRAS and BRAFV600E Mutations in Patients with Lymph-Node-Positive Colon Cancer. / Zaanan, Aziz; Bachet, Jean Baptiste; André, Thierry; Sinicrope, Frank A.

In: Current Colorectal Cancer Reports, 29.06.2014.

Research output: Contribution to journalArticle

@article{feae3ce87a0e4c348fe08553ab20241f,
title = "Prognostic Impact of Deficient DNA Mismatch Repair and KRAS and BRAFV600E Mutations in Patients with Lymph-Node-Positive Colon Cancer",
abstract = "Although tumor stage remains the key determinant of colorectal cancer prognosis and treatment, there is considerable stage-independent variability in clinical outcome. Molecular markers hold promise for explaining variations in clinical behavior, and may identify patient subsets with differential efficacy and survival after adjuvant chemotherapy, which is the standard of care for patients with lymph-node-positive, i.e., stage III, colon cancer. An increased understanding of the molecular evolution and progression of colorectal cancer has identified two major pathways of tumorigenesis that are characterized by chromosomal instability and by microsatellite instability. Microsatellite instability is a consequence of deficient DNA mismatch repair that is generally due to epigenetic inactivation of MLH1 in tumors that often carry mutations (V600E) in oncogenic BRAF. Activating BRAFV600E and KRAS mutations are mutually exclusive, and in this article, we review the current status of these mutations and the mismatch repair status as prognostic biomarkers in stage III colon cancers.",
keywords = "Biomarker, BRAF, Colorectal cancer, KRAS, Microsatellite instability, Prognosis",
author = "Aziz Zaanan and Bachet, {Jean Baptiste} and Thierry Andr{\'e} and Sinicrope, {Frank A}",
year = "2014",
month = "6",
day = "29",
doi = "10.1007/s11888-014-0237-2",
language = "English (US)",
journal = "Current Colorectal Cancer Reports",
issn = "1556-3790",
publisher = "Springer Science + Business Media",

}

TY - JOUR

T1 - Prognostic Impact of Deficient DNA Mismatch Repair and KRAS and BRAFV600E Mutations in Patients with Lymph-Node-Positive Colon Cancer

AU - Zaanan, Aziz

AU - Bachet, Jean Baptiste

AU - André, Thierry

AU - Sinicrope, Frank A

PY - 2014/6/29

Y1 - 2014/6/29

N2 - Although tumor stage remains the key determinant of colorectal cancer prognosis and treatment, there is considerable stage-independent variability in clinical outcome. Molecular markers hold promise for explaining variations in clinical behavior, and may identify patient subsets with differential efficacy and survival after adjuvant chemotherapy, which is the standard of care for patients with lymph-node-positive, i.e., stage III, colon cancer. An increased understanding of the molecular evolution and progression of colorectal cancer has identified two major pathways of tumorigenesis that are characterized by chromosomal instability and by microsatellite instability. Microsatellite instability is a consequence of deficient DNA mismatch repair that is generally due to epigenetic inactivation of MLH1 in tumors that often carry mutations (V600E) in oncogenic BRAF. Activating BRAFV600E and KRAS mutations are mutually exclusive, and in this article, we review the current status of these mutations and the mismatch repair status as prognostic biomarkers in stage III colon cancers.

AB - Although tumor stage remains the key determinant of colorectal cancer prognosis and treatment, there is considerable stage-independent variability in clinical outcome. Molecular markers hold promise for explaining variations in clinical behavior, and may identify patient subsets with differential efficacy and survival after adjuvant chemotherapy, which is the standard of care for patients with lymph-node-positive, i.e., stage III, colon cancer. An increased understanding of the molecular evolution and progression of colorectal cancer has identified two major pathways of tumorigenesis that are characterized by chromosomal instability and by microsatellite instability. Microsatellite instability is a consequence of deficient DNA mismatch repair that is generally due to epigenetic inactivation of MLH1 in tumors that often carry mutations (V600E) in oncogenic BRAF. Activating BRAFV600E and KRAS mutations are mutually exclusive, and in this article, we review the current status of these mutations and the mismatch repair status as prognostic biomarkers in stage III colon cancers.

KW - Biomarker

KW - BRAF

KW - Colorectal cancer

KW - KRAS

KW - Microsatellite instability

KW - Prognosis

UR - http://www.scopus.com/inward/record.url?scp=84903222401&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903222401&partnerID=8YFLogxK

U2 - 10.1007/s11888-014-0237-2

DO - 10.1007/s11888-014-0237-2

M3 - Article

JO - Current Colorectal Cancer Reports

JF - Current Colorectal Cancer Reports

SN - 1556-3790

ER -