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EARLY ONSET HEREDITARY PAPILLARY RENAL CARCINOMA: GERMLINE MISSENSE MUTATIONS IN THE TYROSINE KINASE DOMAIN OF THE MET PROTO-ONCOGENE

2004; Lippincott Williams & Wilkins; Volume: 172; Issue: 4 Part 1 Linguagem: Inglês

10.1097/01.ju.0000139583.63354.e0

1527-3792

Laura S. Schmidt, Michael L. Nickerson, Debora Angeloni, G.M. Glenn, McClellan M. Walther, Paul S. Albert, Michelle B. Warren, Peter L. Choyke, Carlos A. Torres‐Cabala, Maria J. Merino, Joan Brunet, V. Berez, Joan Borràs, G Sesia, Lindsay Middelton, John L. Phillips, Catherine A. Stolle, Berton Zbar, Stephen E. Pautler, W. Marston Linehan,

Epigenetics and DNA Methylation

No AccessJournal of UrologyAdult Urology: Oncology: Renal/Upper Tract/Bladder1 Oct 2004EARLY ONSET HEREDITARY PAPILLARY RENAL CARCINOMA: GERMLINE MISSENSE MUTATIONS IN THE TYROSINE KINASE DOMAIN OF THE MET PROTO-ONCOGENE LAURA S. SCHMIDT, MICHAEL L. NICKERSON, DEBORA ANGELONI, GLADYS M. GLENN, McCLELLAN M. WALTHER, PAUL S. ALBERT, MICHELLE B. WARREN, PETER L. CHOYKE, CARLOS A. TORRES-CABALA, MARIA J. MERINO, JOAN BRUNET, VICTÒRIA BÉREZ, JOAN BORRÀS, GIOVANNI SESIA, LINDSAY MIDDELTON, JOHN L. PHILLIPS, CATHERINE STOLLE, BERTON ZBAR, STEPHEN E. PAUTLER, and W. MARSTON LINEHAN LAURA S. SCHMIDTLAURA S. SCHMIDT , MICHAEL L. NICKERSONMICHAEL L. NICKERSON , DEBORA ANGELONIDEBORA ANGELONI , GLADYS M. GLENNGLADYS M. GLENN , McCLELLAN M. WALTHERMcCLELLAN M. WALTHER , PAUL S. ALBERTPAUL S. ALBERT , MICHELLE B. WARRENMICHELLE B. WARREN , PETER L. CHOYKEPETER L. CHOYKE , CARLOS A. TORRES-CABALACARLOS A. TORRES-CABALA , MARIA J. MERINOMARIA J. MERINO , JOAN BRUNETJOAN BRUNET , VICTÒRIA BÉREZVICTÒRIA BÉREZ , JOAN BORRÀSJOAN BORRÀS , GIOVANNI SESIAGIOVANNI SESIA , LINDSAY MIDDELTONLINDSAY MIDDELTON , JOHN L. PHILLIPSJOHN L. PHILLIPS , CATHERINE STOLLECATHERINE STOLLE , BERTON ZBARBERTON ZBAR , STEPHEN E. PAUTLERSTEPHEN E. PAUTLER , and W. MARSTON LINEHANW. MARSTON LINEHAN View All Author Informationhttps://doi.org/10.1097/01.ju.0000139583.63354.e0AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Hereditary papillary renal carcinoma (HPRC) is characterized by a predisposition to multiple, bilateral papillary type 1 renal tumors caused by inherited activating missense mutations in the tyrosine kinase domain of the MET proto-oncogene. In the current study we evaluated the clinical phenotype and germline MET mutation of 3 new HPRC families. We describe the early onset clinical features of HPRC. Materials and Methods: We identified new HPRC families of Italian (family 177), Spanish (family 223) and Cuban (family 268) descent. We evaluated their clinical features, performed MET mutation analysis by denaturing high performance liquid chromatography and DNA sequencing, and estimated age dependent penetrance and survival using Kaplan-Meier analysis. We characterized renal tumors by histology and fluorescence in situ hybridization. Results: Identical germline MET c.3522G→A mutations (V1110I) were identified in families 177 and 268 but no evidence of a founder effect was found. Affected members of family 223 carried a germline c.3906G→C.3522G→A MET mutation (V1238I). Age dependent penetrance but not survival was significantly earlier for the c.3522G→A mutation than for the c.3906G→A mutation in these HPRC families. Trisomy of chromosome 7 and papillary renal carcinoma type 1 histology were detected in papillary renal tumors. Conclusions: HPRC can occur in an early onset form. The median age for renal tumor development in these 3 HPRC families was 46 to 63 years. HPRC associated papillary renal tumors may be aggressive and metastasize, leading to mortality. Median survival age was 60 to 70 years. Families with identical germline mutations in MET do not always share a common ancestor. HPRC is characterized by germline mutations in MET and papillary type 1 renal tumor histology. References 1 : Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors. Mod Pathol1997; 10: 537. Google Scholar 2 : Hereditary papillary renal carcinoma. J Urol1994; 151: 561. Link, Google Scholar 3 : Hereditary papillary renal cell carcinoma: clinical studies in 10 families. J Urol1995; 153: 907. Link, Google Scholar 4 : Hereditary and sporadic papillary renal carcinomas with c-met mutations share a distinct morphological phenotype. Am J Pathol1999; 155: 517. Google Scholar 5 : Molecular cytogenetics of renal cell tumors. 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Genes Chromosomes Cancer2001; 31: 1. Google Scholar 19 : Signature-based analysis of MET proto-oncogene mutations using DHPLC. Hum Mutat2000; 16: 68. Google Scholar 20 Linehan W.M., Walther M.M., Zbar B.: The genetic basis of cancer in the kidney. J Urol, 170: Google Scholar 21 : Hereditary renal cancers. Radiology2003; 226: 33. Google Scholar From the Basic Research Program, SAIC-Frederick, Inc. (LSS) and Laboratory of Immunobiology, Center for Cancer Research, National Cancer Institute Frederick (MLN, MBW, BZ), Frederick, Urologic Oncology Branch (MMW, LM, JLP, SEP, WML), Diagnostic Radiology (PLC) and Laboratory of Pathology (CAT-C, MJM), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda and Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics (GMG) and Biometric Research Branch, Division of Cancer Treatment and Diagnosis (PSA), National Cancer Institute, Rockville, Maryland, Scuola Superiore Sant'Anna and National Research Council-Institute of Clinical Physiology (DA), Pisa and Corso Duca degli Abruzzi (GS), Torino, Italy, Cancer Risk Evaluation Unit, Catalan Institute of Oncology, Josep Trueta Hospital (JB), Girona and Hospital Sant Joan, Rovira i Virgili University (JB, VB, JB), Reus, Spain, and Molecular Genetics Laboratory, Department of Clinical Laboratories and Pathology, Children's Hospital of Philadelphia (CS), Philadelphia, Pennsylvania© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited ByLaguna M (2018) Re: Defining Early-Onset Kidney Cancer: Implications for Germline and Somatic Mutation Testing and Clinical ManagementJournal of Urology, VOL. 192, NO. 3, (721-722), Online publication date: 1-Sep-2014.Kim C, Vocke C, Torres-Cabala C, Yang Y, Schmidt L, Walther M and Linehan W (2018) Expression of Hypoxia Inducible Factor-1α and 2α in Genetically Distinct Early Renal Cortical TumorsJournal of Urology, VOL. 175, NO. 5, (1908-1914), Online publication date: 1-May-2006. Volume 172Issue 4 Part 1October 2004Page: 1256-1261 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordsproto-oncogene protein c-metneoplastic syndromeshereditarykidneycarcinomarenal cellmutationMetricsAuthor Information LAURA S. SCHMIDT More articles by this author MICHAEL L. NICKERSON More articles by this author DEBORA ANGELONI More articles by this author GLADYS M. GLENN More articles by this author McCLELLAN M. WALTHER More articles by this author PAUL S. ALBERT More articles by this author MICHELLE B. WARREN More articles by this author PETER L. CHOYKE More articles by this author CARLOS A. TORRES-CABALA More articles by this author MARIA J. MERINO More articles by this author JOAN BRUNET More articles by this author VICTÒRIA BÉREZ More articles by this author JOAN BORRÀS More articles by this author GIOVANNI SESIA More articles by this author LINDSAY MIDDELTON More articles by this author JOHN L. PHILLIPS More articles by this author CATHERINE STOLLE More articles by this author BERTON ZBAR More articles by this author STEPHEN E. PAUTLER Current address: University of Western Ontario, London, Ontario, Canada More articles by this author W. MARSTON LINEHAN More articles by this author Expand All Advertisement PDF DownloadLoading ...