Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer

James R. Eshleman; Evan Z. Lang; Gordana K. Bowerfind; Ramon Parsons; Bert Vogelstein; James K.V. Willson; Martina L. Veigl; W. David Sedwick; Sanford D. Markowitz

Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer

James R. Eshleman, Evan Z. Lang, Gordana K. Bowerfind, Ramon Parsons, Bert Vogelstein, James K.V. Willson, Martina L. Veigl, W. David Sedwick, Sanford D. Markowitz

Howard Hughes Medical Institution

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

225 Scopus citations

Abstract

Hereditary Non-Polyposis Colon Cancer (HNPCC) tumors and some sporadic colon cancers acquire somatic changes in the length of microsatellite sequences. We hypothesized that this 'replication error' (RER) phenotype in these cancers reflects a more general defect which should result in hypermutability of expressed genes. To test this hypothesis mutations of hprt were studied in RER and non-RER tumor cell lines. Increased mutation rates of greater than 100-fold were found in RER compared to non-RER lines. Heterogeneity within the RER group suggests the likely existence of different classes of RER tumors. One non-RER cell demonstrated a greater than 10-fold increase mutation rate, suggesting that a novel mutator phenotype may exist in some non-RER tumors.

Original language	English (US)
Pages (from-to)	33-37
Number of pages	5
Journal	Oncogene
Volume	10
Issue number	1
State	Published - Jan 5 1995

Keywords

Colon cancer
Genomic instability
HNPCC (hereditary nonpolyposis colon cancer)
HPRT
Replication errors (RER)

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

Cite this

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title = "Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer",

abstract = "Hereditary Non-Polyposis Colon Cancer (HNPCC) tumors and some sporadic colon cancers acquire somatic changes in the length of microsatellite sequences. We hypothesized that this 'replication error' (RER) phenotype in these cancers reflects a more general defect which should result in hypermutability of expressed genes. To test this hypothesis mutations of hprt were studied in RER and non-RER tumor cell lines. Increased mutation rates of greater than 100-fold were found in RER compared to non-RER lines. Heterogeneity within the RER group suggests the likely existence of different classes of RER tumors. One non-RER cell demonstrated a greater than 10-fold increase mutation rate, suggesting that a novel mutator phenotype may exist in some non-RER tumors.",

keywords = "Colon cancer, Genomic instability, HNPCC (hereditary nonpolyposis colon cancer), HPRT, Replication errors (RER)",

author = "Eshleman, {James R.} and Lang, {Evan Z.} and Bowerfind, {Gordana K.} and Ramon Parsons and Bert Vogelstein and Willson, {James K.V.} and Veigl, {Martina L.} and Sedwick, {W. David} and Markowitz, {Sanford D.}",

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T1 - Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer

AU - Eshleman, James R.

AU - Lang, Evan Z.

AU - Bowerfind, Gordana K.

AU - Parsons, Ramon

AU - Vogelstein, Bert

AU - Willson, James K.V.

AU - Veigl, Martina L.

AU - Sedwick, W. David

AU - Markowitz, Sanford D.

PY - 1995/1/5

Y1 - 1995/1/5

N2 - Hereditary Non-Polyposis Colon Cancer (HNPCC) tumors and some sporadic colon cancers acquire somatic changes in the length of microsatellite sequences. We hypothesized that this 'replication error' (RER) phenotype in these cancers reflects a more general defect which should result in hypermutability of expressed genes. To test this hypothesis mutations of hprt were studied in RER and non-RER tumor cell lines. Increased mutation rates of greater than 100-fold were found in RER compared to non-RER lines. Heterogeneity within the RER group suggests the likely existence of different classes of RER tumors. One non-RER cell demonstrated a greater than 10-fold increase mutation rate, suggesting that a novel mutator phenotype may exist in some non-RER tumors.

AB - Hereditary Non-Polyposis Colon Cancer (HNPCC) tumors and some sporadic colon cancers acquire somatic changes in the length of microsatellite sequences. We hypothesized that this 'replication error' (RER) phenotype in these cancers reflects a more general defect which should result in hypermutability of expressed genes. To test this hypothesis mutations of hprt were studied in RER and non-RER tumor cell lines. Increased mutation rates of greater than 100-fold were found in RER compared to non-RER lines. Heterogeneity within the RER group suggests the likely existence of different classes of RER tumors. One non-RER cell demonstrated a greater than 10-fold increase mutation rate, suggesting that a novel mutator phenotype may exist in some non-RER tumors.

KW - Colon cancer

KW - Genomic instability

KW - HNPCC (hereditary nonpolyposis colon cancer)

KW - HPRT

KW - Replication errors (RER)

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Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer

Abstract

Keywords

ASJC Scopus subject areas

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