Papillary renal cell carcinoma: Analysis of germline mutations in the MET proto-oncogene in a clinic-based population

Noralane Morey Lindor, C. B. Dechet, M. H. Greene, Robert Brian Jenkins, M. T. Zincke, A. L. Weaver, M. Wilson, H. Zincke, W. Liu

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Approximately 10% of all renal cell carcinomas (RCCs) present a distinctive papillary histology. Familial papillary RCC (PRCC) has been described, but the majority of cases appear to be sporadic. Recently, germline mutations in the MET proto-oncogene on chromosome 7 have been identified in families with hereditary PRCC. We evaluated 59 patients with PRCC for the frequency of MET germline mutations to determine the value of genetic screening of this patient population. Between 1976 and 1997, 165 patients were identified with PRCC by retrospective chart review. Fifty-nine of 133 surviving patients agreed to provide a family history, a blood specimen, and informed consent for genetic research. DNA was isolated from peripheral blood leukocytes. Denaturing high-performance liquid chromatography (DHPLC) followed by genomic sequencing was performed on eight exons of the MET proto-oncogene, including exons 5-7 of the extracellular domain, exon 14, and exons 16-19 of the tyrosine kinase domain. The 59 patients in this study included 49 men and 10 women with a mean age at diagnosis of 61 years. Bilateral and/or multifocal disease was present in 13 cases (22%). No germline mutations were detected in the studied exons of the MET proto-oncogene (exons previously reported to contain deleterious mutations in familial PRCC). No pathological MET proto-oncogene germline mutations were identified in 59 patients with PRCC. The germline mutation rate in this clinic-based population of individuals with PRCC approaches 0% (CI = 0-6.18). MET proto-oncogene germline mutation screening does not appear to be clinically indicated in patients with PRCC without additional evidence for a genetic predisposition (positive family history, unusual age at onset, bilateral disease).

Original languageEnglish (US)
Pages (from-to)101-106
Number of pages6
JournalGenetic Testing
Volume5
Issue number2
StatePublished - 2001

Fingerprint

Proto-Oncogenes
Germ-Line Mutation
Renal Cell Carcinoma
Exons
Population
Genetic Research
Chromosomes, Human, Pair 7
Genetic Testing
Mutation Rate
Genetic Predisposition to Disease
Informed Consent
Age of Onset
Protein-Tyrosine Kinases
Histology
Leukocytes
High Pressure Liquid Chromatography
Mutation
DNA

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Papillary renal cell carcinoma : Analysis of germline mutations in the MET proto-oncogene in a clinic-based population. / Lindor, Noralane Morey; Dechet, C. B.; Greene, M. H.; Jenkins, Robert Brian; Zincke, M. T.; Weaver, A. L.; Wilson, M.; Zincke, H.; Liu, W.

In: Genetic Testing, Vol. 5, No. 2, 2001, p. 101-106.

Research output: Contribution to journalArticle

Lindor, NM, Dechet, CB, Greene, MH, Jenkins, RB, Zincke, MT, Weaver, AL, Wilson, M, Zincke, H & Liu, W 2001, 'Papillary renal cell carcinoma: Analysis of germline mutations in the MET proto-oncogene in a clinic-based population', Genetic Testing, vol. 5, no. 2, pp. 101-106.
Lindor, Noralane Morey ; Dechet, C. B. ; Greene, M. H. ; Jenkins, Robert Brian ; Zincke, M. T. ; Weaver, A. L. ; Wilson, M. ; Zincke, H. ; Liu, W. / Papillary renal cell carcinoma : Analysis of germline mutations in the MET proto-oncogene in a clinic-based population. In: Genetic Testing. 2001 ; Vol. 5, No. 2. pp. 101-106.
@article{f2110be1af77452b9464ab92324d67e9,
title = "Papillary renal cell carcinoma: Analysis of germline mutations in the MET proto-oncogene in a clinic-based population",
abstract = "Approximately 10{\%} of all renal cell carcinomas (RCCs) present a distinctive papillary histology. Familial papillary RCC (PRCC) has been described, but the majority of cases appear to be sporadic. Recently, germline mutations in the MET proto-oncogene on chromosome 7 have been identified in families with hereditary PRCC. We evaluated 59 patients with PRCC for the frequency of MET germline mutations to determine the value of genetic screening of this patient population. Between 1976 and 1997, 165 patients were identified with PRCC by retrospective chart review. Fifty-nine of 133 surviving patients agreed to provide a family history, a blood specimen, and informed consent for genetic research. DNA was isolated from peripheral blood leukocytes. Denaturing high-performance liquid chromatography (DHPLC) followed by genomic sequencing was performed on eight exons of the MET proto-oncogene, including exons 5-7 of the extracellular domain, exon 14, and exons 16-19 of the tyrosine kinase domain. The 59 patients in this study included 49 men and 10 women with a mean age at diagnosis of 61 years. Bilateral and/or multifocal disease was present in 13 cases (22{\%}). No germline mutations were detected in the studied exons of the MET proto-oncogene (exons previously reported to contain deleterious mutations in familial PRCC). No pathological MET proto-oncogene germline mutations were identified in 59 patients with PRCC. The germline mutation rate in this clinic-based population of individuals with PRCC approaches 0{\%} (CI = 0-6.18). MET proto-oncogene germline mutation screening does not appear to be clinically indicated in patients with PRCC without additional evidence for a genetic predisposition (positive family history, unusual age at onset, bilateral disease).",
author = "Lindor, {Noralane Morey} and Dechet, {C. B.} and Greene, {M. H.} and Jenkins, {Robert Brian} and Zincke, {M. T.} and Weaver, {A. L.} and M. Wilson and H. Zincke and W. Liu",
year = "2001",
language = "English (US)",
volume = "5",
pages = "101--106",
journal = "Genetic Testing and Molecular Biomarkers",
issn = "1945-0265",
publisher = "Mary Ann Liebert Inc.",
number = "2",

}

TY - JOUR

T1 - Papillary renal cell carcinoma

T2 - Analysis of germline mutations in the MET proto-oncogene in a clinic-based population

AU - Lindor, Noralane Morey

AU - Dechet, C. B.

AU - Greene, M. H.

AU - Jenkins, Robert Brian

AU - Zincke, M. T.

AU - Weaver, A. L.

AU - Wilson, M.

AU - Zincke, H.

AU - Liu, W.

PY - 2001

Y1 - 2001

N2 - Approximately 10% of all renal cell carcinomas (RCCs) present a distinctive papillary histology. Familial papillary RCC (PRCC) has been described, but the majority of cases appear to be sporadic. Recently, germline mutations in the MET proto-oncogene on chromosome 7 have been identified in families with hereditary PRCC. We evaluated 59 patients with PRCC for the frequency of MET germline mutations to determine the value of genetic screening of this patient population. Between 1976 and 1997, 165 patients were identified with PRCC by retrospective chart review. Fifty-nine of 133 surviving patients agreed to provide a family history, a blood specimen, and informed consent for genetic research. DNA was isolated from peripheral blood leukocytes. Denaturing high-performance liquid chromatography (DHPLC) followed by genomic sequencing was performed on eight exons of the MET proto-oncogene, including exons 5-7 of the extracellular domain, exon 14, and exons 16-19 of the tyrosine kinase domain. The 59 patients in this study included 49 men and 10 women with a mean age at diagnosis of 61 years. Bilateral and/or multifocal disease was present in 13 cases (22%). No germline mutations were detected in the studied exons of the MET proto-oncogene (exons previously reported to contain deleterious mutations in familial PRCC). No pathological MET proto-oncogene germline mutations were identified in 59 patients with PRCC. The germline mutation rate in this clinic-based population of individuals with PRCC approaches 0% (CI = 0-6.18). MET proto-oncogene germline mutation screening does not appear to be clinically indicated in patients with PRCC without additional evidence for a genetic predisposition (positive family history, unusual age at onset, bilateral disease).

AB - Approximately 10% of all renal cell carcinomas (RCCs) present a distinctive papillary histology. Familial papillary RCC (PRCC) has been described, but the majority of cases appear to be sporadic. Recently, germline mutations in the MET proto-oncogene on chromosome 7 have been identified in families with hereditary PRCC. We evaluated 59 patients with PRCC for the frequency of MET germline mutations to determine the value of genetic screening of this patient population. Between 1976 and 1997, 165 patients were identified with PRCC by retrospective chart review. Fifty-nine of 133 surviving patients agreed to provide a family history, a blood specimen, and informed consent for genetic research. DNA was isolated from peripheral blood leukocytes. Denaturing high-performance liquid chromatography (DHPLC) followed by genomic sequencing was performed on eight exons of the MET proto-oncogene, including exons 5-7 of the extracellular domain, exon 14, and exons 16-19 of the tyrosine kinase domain. The 59 patients in this study included 49 men and 10 women with a mean age at diagnosis of 61 years. Bilateral and/or multifocal disease was present in 13 cases (22%). No germline mutations were detected in the studied exons of the MET proto-oncogene (exons previously reported to contain deleterious mutations in familial PRCC). No pathological MET proto-oncogene germline mutations were identified in 59 patients with PRCC. The germline mutation rate in this clinic-based population of individuals with PRCC approaches 0% (CI = 0-6.18). MET proto-oncogene germline mutation screening does not appear to be clinically indicated in patients with PRCC without additional evidence for a genetic predisposition (positive family history, unusual age at onset, bilateral disease).

UR - http://www.scopus.com/inward/record.url?scp=0034869788&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034869788&partnerID=8YFLogxK

M3 - Article

C2 - 11551094

AN - SCOPUS:0034869788

VL - 5

SP - 101

EP - 106

JO - Genetic Testing and Molecular Biomarkers

JF - Genetic Testing and Molecular Biomarkers

SN - 1945-0265

IS - 2

ER -