Replication Errors in Benign and Malignant Tumors from Hereditary Nonpolyposis Colorectal Cancer Patients

Aaltonen, Lauri A.; Peltomäki, Päivi; Mecklin, Jukka-Pekka; Järvinen, Heikki; Jass, Jeremy R.; Green, Jane S.; Lynch, Henry T.; Watson, Patrice; Tallqvist, Gustav; Juhola, Matti; Sistonen, Pertti; Hamilton, Stanley R.; Kinzler, Kenneth W.; Vogelstein, Bert; de la Chapelle, Albert

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Articles| April 01 1994

Replication Errors in Benign and Malignant Tumors from Hereditary Nonpolyposis Colorectal Cancer Patients^¹

Lauri A. Aaltonen;

Lauri A. Aaltonen

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Päivi Peltomäki;

Päivi Peltomäki

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Jukka-Pekka Mecklin;

Jukka-Pekka Mecklin

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Heikki Järvinen;

Heikki Järvinen

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Jeremy R. Jass;

Jeremy R. Jass

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Jane S. Green;

Jane S. Green

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Henry T. Lynch;

Henry T. Lynch

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Patrice Watson;

Patrice Watson

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Gustav Tallqvist;

Gustav Tallqvist

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Matti Juhola;

Matti Juhola

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Pertti Sistonen;

Pertti Sistonen

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Stanley R. Hamilton;

Stanley R. Hamilton

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Kenneth W. Kinzler;

Kenneth W. Kinzler

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Bert Vogelstein;

Bert Vogelstein

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Albert de la Chapelle

Department of Medical Genetics, University of Helsinki

,

FIN-00014 Helsinki

,

Finland

[L. A. A., P. P., G. T., P. S., A. d. l. C.];

Departments of Surgery and Pathology, Jyväskylä Central Hospital

,

40620 Jyväskylä

,

Finland

[J-P. M., M. J.];

Second Department of Surgery, Helsinki University Central Hospital

,

00290 Helsinki

,

Finland

[H. J.];

Department of Pathology, University of Auckland School of Medicine

,

Auckland

,

New Zealand

[J. R. J.];

Faculty of Medicine, Memorial University of Newfoundland, St. John's

,

Newfoundland

,

Canada

A1B3V6 [J. S. G.];

Department of Preventive Medicine, Creighton University School of Medicine

,

Omaha, Nebraska 68178 [H. T. L., P. W.]

;

Department of Pathology, the Johns Hopkins University Schools of Medicine

,

Baltimore, Maryland 21205 [S. R. H.]

; and the

Johns Hopkins Oncology Center

,

Baltimore, Maryland 21231 [K. W. K., B. V.]

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Author & Article Information

²

To whom requests for reprints should be addressed, at Department of Medical Genetics, University of Helsinki, P. O. Box 21, Haartmaninkatu 3, FIN-00014 Helsinki.

Received: January 18 1994

Accepted: February 22 1994

Online ISSN: 1538-7445

Print ISSN: 0008-5472

1994

American Association for Cancer Research, Inc.

Cancer Res (1994) 54 (7): 1645–1648.

Abstract

A replication error (RER) phenotype has been documented both in sporadic colorectal tumors and in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). In the current study 8 of 49 (16%) sporadic colorectal cancers (CRCs) and 25 of 29 (86%) CRCs from HNPCC patients were found to be RER+. All 9 (100%) CRCs from HNPCC patients with germline mutations of the mismatch repair gene MSH2 were found to be RER+, while 16 of 20 CRCs from HNPCC kindreds unlinked or not studied for linkage to MSH2 were RER+. Corresponding analysis in colorectal adenomas revealed that only 1 of 33 (3%) sporadic tumors but 8 of 14 (57%) HNPCC tumors were RER+. Moreover, RER was found in all 6 extracolonic cancers (endometrium, 2; kidney, 1; stomach, 1; duodenum, 1; and ovary, 1) derived from members of HNPCC families. These data suggest the involvement of mismatch repair deficiency in the premalignant stage of tumorigenesis in HNPCC cases, and suggest that mismatch repair genes (MSH2 or others) are defective in the germline of nearly all these patients.

¹

Part of this study was conducted at the Folkhälsan Institute of Genetics. Supported by grants from the Academy of Finland, the Finnish Cancer Society, the Sigrid Juselius Foundation, the Ida Montin Foundation, the Finnish Foundation for Gastroenterological Research, the Duodecim Foundation, the Research and Science Foundation of Farmos, the Cancer Society and Health Research Council of New Zealand, the Clayton Fund, NIH Grant CA 35494, and the Council for Tobacco Research Grant 1297-DR2.

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1994

American Association for Cancer Research, Inc.

Replication Errors in Benign and Malignant Tumors from Hereditary Nonpolyposis Colorectal Cancer Patients^¹

Abstract

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Replication Errors in Benign and Malignant Tumors from Hereditary Nonpolyposis Colorectal Cancer Patients1

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Replication Errors in Benign and Malignant Tumors from Hereditary Nonpolyposis Colorectal Cancer Patients^¹