Microsatellite instability and loss of heterozygosity at chromosomal location 18q: Pospective evaluation of biomarkers for stages II and III colon cancer - A study of CALGB 9581 and 89803

Monica M. Bertagnolli, Mark Redston, Carolyn Compton, Donna Niedzwiecki, Robert J. Mayer, Richard M. Goldberg, Thomas A. Colacchio, Leonard B. Saltz, Robert S. Warren

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Purpose: Colorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors. Patients and Methods: We studied two of these genomic defects - mismatch repair deficiency (MMR-D) and loss of heterozygosity at chromosomal location 18q (18qLOH) - in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer. These trials included prospective secondary analyses to determine the relationship between these markers and treatment outcome. A total of 1,852 patients were tested for MMR status and 955 (excluding patients with MMR-D tumors) for 18qLOH. Results: Compared with stage III, more stage II tumors were MMR-D (21.3% v 14.4%; P < .001) and were intact at 18q (24.2% v 15.1%; P = .001). For the combined cohort, patients with MMR-D tumors had better 5-year disease-free survival (DFS; 0.76 v 0.67; P < .001) and overall survival (OS; 0.81 v 0.78; P = .029) than those with MMR intact (MMR-I) tumors. Among patients with MMR-I tumors, the status of 18q did not affect outcome, with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 (P = .18) for DFS and 0.81 versus 0.77 (P = .18) for OS. Conclusion: We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer.

Original languageEnglish (US)
Pages (from-to)3153-3162
Number of pages10
JournalJournal of Clinical Oncology
Volume29
Issue number23
DOIs
StatePublished - Aug 10 2011
Externally publishedYes

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Microsatellite Instability
Loss of Heterozygosity
Colonic Neoplasms
Biomarkers
Neoplasms
Colorectal Neoplasms
Tumor Suppressor Genes
Oncogenes
Disease-Free Survival
Turcot syndrome
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Microsatellite instability and loss of heterozygosity at chromosomal location 18q : Pospective evaluation of biomarkers for stages II and III colon cancer - A study of CALGB 9581 and 89803. / Bertagnolli, Monica M.; Redston, Mark; Compton, Carolyn; Niedzwiecki, Donna; Mayer, Robert J.; Goldberg, Richard M.; Colacchio, Thomas A.; Saltz, Leonard B.; Warren, Robert S.

In: Journal of Clinical Oncology, Vol. 29, No. 23, 10.08.2011, p. 3153-3162.

Research output: Contribution to journalArticle

Bertagnolli, Monica M. ; Redston, Mark ; Compton, Carolyn ; Niedzwiecki, Donna ; Mayer, Robert J. ; Goldberg, Richard M. ; Colacchio, Thomas A. ; Saltz, Leonard B. ; Warren, Robert S. / Microsatellite instability and loss of heterozygosity at chromosomal location 18q : Pospective evaluation of biomarkers for stages II and III colon cancer - A study of CALGB 9581 and 89803. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 23. pp. 3153-3162.
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abstract = "Purpose: Colorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors. Patients and Methods: We studied two of these genomic defects - mismatch repair deficiency (MMR-D) and loss of heterozygosity at chromosomal location 18q (18qLOH) - in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer. These trials included prospective secondary analyses to determine the relationship between these markers and treatment outcome. A total of 1,852 patients were tested for MMR status and 955 (excluding patients with MMR-D tumors) for 18qLOH. Results: Compared with stage III, more stage II tumors were MMR-D (21.3{\%} v 14.4{\%}; P < .001) and were intact at 18q (24.2{\%} v 15.1{\%}; P = .001). For the combined cohort, patients with MMR-D tumors had better 5-year disease-free survival (DFS; 0.76 v 0.67; P < .001) and overall survival (OS; 0.81 v 0.78; P = .029) than those with MMR intact (MMR-I) tumors. Among patients with MMR-I tumors, the status of 18q did not affect outcome, with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 (P = .18) for DFS and 0.81 versus 0.77 (P = .18) for OS. Conclusion: We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer.",
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T1 - Microsatellite instability and loss of heterozygosity at chromosomal location 18q

T2 - Pospective evaluation of biomarkers for stages II and III colon cancer - A study of CALGB 9581 and 89803

AU - Bertagnolli, Monica M.

AU - Redston, Mark

AU - Compton, Carolyn

AU - Niedzwiecki, Donna

AU - Mayer, Robert J.

AU - Goldberg, Richard M.

AU - Colacchio, Thomas A.

AU - Saltz, Leonard B.

AU - Warren, Robert S.

PY - 2011/8/10

Y1 - 2011/8/10

N2 - Purpose: Colorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors. Patients and Methods: We studied two of these genomic defects - mismatch repair deficiency (MMR-D) and loss of heterozygosity at chromosomal location 18q (18qLOH) - in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer. These trials included prospective secondary analyses to determine the relationship between these markers and treatment outcome. A total of 1,852 patients were tested for MMR status and 955 (excluding patients with MMR-D tumors) for 18qLOH. Results: Compared with stage III, more stage II tumors were MMR-D (21.3% v 14.4%; P < .001) and were intact at 18q (24.2% v 15.1%; P = .001). For the combined cohort, patients with MMR-D tumors had better 5-year disease-free survival (DFS; 0.76 v 0.67; P < .001) and overall survival (OS; 0.81 v 0.78; P = .029) than those with MMR intact (MMR-I) tumors. Among patients with MMR-I tumors, the status of 18q did not affect outcome, with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 (P = .18) for DFS and 0.81 versus 0.77 (P = .18) for OS. Conclusion: We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer.

AB - Purpose: Colorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors. Patients and Methods: We studied two of these genomic defects - mismatch repair deficiency (MMR-D) and loss of heterozygosity at chromosomal location 18q (18qLOH) - in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer. These trials included prospective secondary analyses to determine the relationship between these markers and treatment outcome. A total of 1,852 patients were tested for MMR status and 955 (excluding patients with MMR-D tumors) for 18qLOH. Results: Compared with stage III, more stage II tumors were MMR-D (21.3% v 14.4%; P < .001) and were intact at 18q (24.2% v 15.1%; P = .001). For the combined cohort, patients with MMR-D tumors had better 5-year disease-free survival (DFS; 0.76 v 0.67; P < .001) and overall survival (OS; 0.81 v 0.78; P = .029) than those with MMR intact (MMR-I) tumors. Among patients with MMR-I tumors, the status of 18q did not affect outcome, with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 (P = .18) for DFS and 0.81 versus 0.77 (P = .18) for OS. Conclusion: We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer.

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