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February 15, 1995, Vol 273, No. 7 >
ARTICLE | February 15, 1995

Identification of the von Hippel-Lindau (VHL) Gene: Title and subTitle BreakIts Role in Renal Cancer FREE

W. Marston Linehan, MD; Michael I. Lerman, MD, PhD; Berton Zbar, MD
[+] Author Affiliations

Reprint requests to Urologic Oncology Section, Surgery Branch, Clinical Oncology Program, Division of Cancer Therapy, National Cancer Institute, Bldg 10, Room 2B47, 10 Center DR MSC 1502, Bethesda, MD 20892-1502 (Dr Linehan).


JAMA. 1995;273(7):564-570. doi:10.1001/jama.1995.03520310062031
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Article
References

RENAL carcinoma, the most common cancer of the kidney, occurs in over 27000 individuals in the United States each year and is responsible for over 11000 deaths annually.1 The incidence of renal carcinoma worldwide has been increasing at an annual rate of approximately 2%.1 Although renal carcinoma has been reported in children as young as 3 years, it most commonly occurs in adults between the ages of 50 and 70 years.2 Renal carcinoma affects males twice as frequently as females and accounts for approximately 3% of adult cancers. Although a number of hormonal, environmental, cellular, and genetic factors have been evaluated, little is known about the etiology of renal cancer.3 There is an increased incidence of renal cancer among workers exposed to asbestos and among leather workers,4,5 and a strong correlation has been found with cigarette smoking.6,7 In patients with end-stage renal disease, particularly

REFERENCES

1 +
Boring CC, Squires TS, Tong T.  Cancer statistics. CA Cancer J Clin . 1994;;44:7-26.
2 +
Linehan WM, Shipley W, Parkinson D.  Cancer of the kidney and ureter.  In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practices of Oncology . Philadelphia, Pa: JB Lippincott Co; 1993;:1023-1051.
3 +
Reiter R, Zbar B, Linehan WM.  Molecular genetic studies of renal cell carcinoma: potential biologic and clinical significance for genitourinary malignancy.  In: Walsh PC, Retik AB, Vaughan ED, Stamey TA, eds. Campbell's Urology: Update 7 . Philadelphia, Pa: WB Saunders; 1993;:1-15.
4 +
Malker HR, Malker BK, McLaughlin JK, Blot WJ.  Kidney cancer among leather workers. Lancet . 1984;;1:56-57.
5 +
Maclure M.  Asbestos and renal adenocarcinoma: a case-control study. Environ Res . 1987;;42:353-361.
6 +
La Vecchia C, Negri E, D'Avanzo B, Franceschi S.  Smoking and renal cell carcinoma. Cancer Res . 1990;;50:5231-5233.
7 +
Yu MC, Mack TM, Hanisch R, Cicioni C, Henderson BE.  Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma. J Nati Cancer Inst . 1986;;77:351-356.
8 +
Chung-Park M, Parveen T, Lam M.  Acquired cystic disease of the kidneys and renal cell carcinoma in chronic renal insufficiency without dialysis treatment. Nephron . 1989;;53:157-161.
9 +
Matson MA, Cohen EP.  Acquired cystic kidney disease: occurrence, prevalence, and renal cancers. Medicine (Baltimore) . 1990;;69:217-226.
10 +
Brennan JF, Stilmant MM, Babayan RK, Siroky MB.  Acquired renal cystic disease: implications for the urologist. Br J Urol . 1991;;67:342-348.
11 +
Kovacs G, Ishikawa I.  High incidence of papillary renal cell tumours in patients on chronic haemodialysis. Histopathology . 1993;;22:135-139.
12 +
Bard RH, Lord B, Fromowitz F.  Papillary adenocarcinoma of kidney. Urology . 1982;;19:16-20.
13 +
Mellemgaard A, Engholm G, McLaughlin JK, Olsen JH.  Risk factors for renal cell carcinoma in Denmark, I: role of socioeconomic status, tobacco use, beverages, and family history. Cancer Causes Control . 1994;;5:105-113.
14 +
Harris H, Miller OJ, Klein G, Worst P, Tachibana T.  Suppression of malignancy by cell fusion. Nature . 1969;;223:363-368.
15 +
Stanbridge EJ.  Suppression of malignancy in human cells. Nature . 1976;;260:17-20.
16 +
Knudson AG Jr.  Antioncogenes and human cancer. Proc Natl Acad Sci U S A . 1993;;90:10914-10921.
17 +
Comings DE.  A general theory of carcinogenesis. Proc Natl Acad Sci U S A . 1973;;70:3324-3328.
18 +
Knudson AG Jr.  Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A . 1971;;68:820-823.
19 +
Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GAP.  Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature . 1990;;343:774-778.
20 +
Cavenee WK, Hansen MF, Nordenskjold M, et al.  Genetic origin of mutations predisposing to retinoblastoma. Science . 1985;;228:501-503.
21 +
Fung Y-KT, Murphree AL, T'Ang A, Quin J, Hinrichs SH, Benedict WF.  Structural evidence for the authenticity of the human retinoblastoma gene. Science . 1987;;236:1657-1661.
22 +
Xu G, O'Connell P, Viskochil D, et al.  The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell . 1990;;62:599-608.
23 +
Kinzler KW, Vogelstein B.  A gene for neurofibromatosis 2. Nature . 1993;;363:495.
24 +
Cohen AJ, Li FP, Berg S, et al.  Hereditary renal-cell carcinoma associated with a chromosomal translocation. N Engl J Med . 1979;;301:592-595.
25 +
Kovacs G, Brusa P, de Riese W.  Tissue-specific expression of a constitutional 3;6 translocation: development of multiple bilateral renal-cell carcinomas. Int J Cancer . 1989;;43:422-427.
26 +
Glenn GM, Choyke PL, Zbar B, Linehan WM.  Von Hippel-Lindau disease: clinical review and molecular genetics.  In: Anderson EE, ed: Problems in Urologic Surgery: Benign and Malignant Tumors of the Kidney . Philadelphia, Pa: JB Lippincott Co; 1990;:312-330.
27 +
Melmon KL, Rosen SW.  Lindau's disease: review of the literature and study of a large kindred. Am J Med . 1964;;36:595-617.
28 +
Zbar B, Tory K, Merino M, et al.  Hereditary papillary renal cell carcinoma. J Urol . 1994;;151: 561-566.
29 +
Zbar B, Glenn G, Lubensky I, et al.  Hereditary papillary renal cell carcinoma: clinical studies in 10 families. J Urol . In press.
30 +
Pathak S, Strong LC, Ferrell RE, Trindade A.  Familial renal cell carcinoma with a 3:11 chromosome translocation limited to tumor cells. Science . 1982;;217:939-941.
31 +
Zbar B.  Chromosomal deletions in lung cancer and renal cancer.  In: DeVita VT, Hellman S, Rosenberg SA, eds. Important Advances in Oncology 1989 . Philadelphia, Pa: JB Lippincott Co; 1989;:41-60.
32 +
Yoshida HA, Ohyashiki K, Ochi H, et al.  Cytogenetic studies of tumor tissue from patients with nonfamilial renal cell carcinoma. Cancer Res . 1986;; 46:2139-2147.
33 +
de Jong B, Oosterhuis JW, Idenburg VJ, Castedo SM, Dam A, Mensink HJ.  Cytogenetics of 12 cases of renal adenocarcinoma. Cancer Genet Cytogenet . 1988;;30:53-61.
34 +
Presti JC, Rao PH, Chen Q, et al.  Histopathological, cytogenetic, and molecular characterization of renal cortical tumors. Cancer Res . 1991;;51:1544-1552.
35 +
Zbar B, Brauch H, Talmadge C, Linehan M.  Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. Nature . 1987;;327: 721-724.
36 +
Kovacs G, Erlandsson R, Boldog F, et al.  Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc Natl Acad Sci US A . 1988;;85:1571-1575.
37 +
Kovacs G, Wilkens L, Papp T, de Riese W.  Differentiation between papillary and nonpapillary renal cell carcinomas by DNA analysis. J Natl Cancer Inst . 1989;;81:527-530.
38 +
Anglard P, Brauch TH, Weiss GH, et al.  Molecular analysis of genetic changes in the origin and development of renal cell carcinoma. Cancer Res . 1991;;51:1071-1077.
39 +
Boldog F, Arheden K, Imreh S, et al.  Involvement of 3p deletions in sporadic and hereditary forms of renal cell carcinoma. Genes Chromosom Cancer . 1991;;3:403-406.
40 +
Morita R, Ishikawa J, Tsutsumi M, et al.  Allelotype of renal cell carcinoma. Cancer Res . 1991;; 51:820-823.
41 +
Ogawa O, Kakehi Y, Ogawa K, Koshiba M, Sugiyama T, Yoshida O.  Allelic loss at chromosome 3p characterizes clear cell phenotype of renal cell carcinoma. Cancer Res . 1991;;51:949-953.
42 +
Yamakawa K, Morita R, Takahashi E, Hori T, Ishikawa J, Nakamura Y.  A detailed deletion mapping of the short arm of chromosome 3 in sporadic renal cell carcinoma. Cancer Res . 1991;;51:4707-4711.
43 +
Szucs S, Muller-Brechlin R, DeRiese W, Kovacs G.  Deletion 3p: the only chromosome loss in a primary renal cell carcinoma. Cancer Genet Cytogenet . 1987;;26:369-373.
44 +
Kovacs G, Frisch S.  Clonal chromosome abnormalities in tumor cells from patients with sporadic renal cell carcinomas. Cancer Res . 1989;;49:651-659.
45 +
Carroll PR, Murty VVS, Reuter V, et al.  Abnormalities of chromosome region 3p12-14 characterize clear cell renal carcinoma. Cancer Genet Cytogenet . 1987;;26:253-259.
46 +
Brooks JD, Bova GS, Marshall FF, Isaacs WB.  Tumor suppressor gene allelic loss in human renal cancers. J Urol . 1993;;150:1278-1283.
47 +
van der Hout AH, van den Berg E, van den Vlies P, et al.  Loss of heterozygosity at the short arm of chromosome 3 in renal-cell cancer correlates with the cytological tumour type. Int J Cancer . 1993;;53:353-357.
48 +
Linehan WM, et al.  Genetic basis of renal cell cancer.  In: DeVita VT, Hellman S, Rosenberg SA, eds. Important Advances in Oncology, 1993 . Philadelphia, Pa: JB Lippincott Co; 1993;:47-70.
49 +
Maher ER, Iselius L, Yates JR, et al.  Von Hippel-Lindau disease: a genetic study. J Med Genet . 1991;;28:443-447.
50 +
Poston CD, Jaffe GS, Solomon D, Zbar B, Linehan WM, Walther MM.  Characterization of the renal pathology of a familial form of renal cell carcinoma associated with von Hippel-Lindau disease: clinical and molecular genetic implications. J Urol . In press.
51 +
Tory K, Brauch H, Linehan M, et al.  Specific genetic change in tumors associated with von Hippel-Lindau disease. J Natl Cancer Inst . 1989;;81:1097-1101.
52 +
Seizinger BR, Rouleau GA, Ozelius LJ, et al.  Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature . 1988;;332:268-269.
53 +
Lerman MI, Latif F, Glenn GM, et al.  Isolation and regional localization of a large collection (2,000) of single copy DNA fragments on human chromosome 3 for mapping and cloning tumor suppressor genes. Hum Genet . 1991;;86:567-577.
54 +
Hosoe S, Brauch H, Latif F, et al.  Localization of the von Hippel-Lindau disease gene to a small region of chromosome 3. Genomics . 1990;;8:634-640.
55 +
Glenn GM, Daniel LN, Choyke P, et al.  Von Hippel-Lindau disease: distinct phenotypes suggest more than one mutant allele at the VHL locus. Hum Genet . 1991;;87:207-210.
56 +
Glenn GM, Linehan WM, Hosoe S, et al.  Screening for von Hippel-Lindau disease by DNA-polymorphism analysis. JAMA . 1992;;267:1226-1231.
57 +
Gnarra JR, Tory K, Weng Y, et al.  Mutation of the VHL tumour suppressor gene in renal carcinoma. Nat Genet . 1994;;7:85-90.
58 +
Yao M, Latif F, Kuzmin I, et al.  Von Hippel-Lindau disease: identification of deletion mutations by pulsed field gel electrophoresis. Hum Genet . 1993;;92:605-614.
59 +
Latif F, Tory K, Gnarra J, et al.  Identification of the von Hippel-Lindau disease tumor suppressor gene. Science . 1993;;260:1317-1320.
60 +
Chen F, Kishida T, Yao M, et al.  Germ-line mutations in the von Hippel-Lindau disease tumor suppressor gene: correlation with phenotype. Hum Mutat . In press.
61 +
Whaley JM, Naglich J, Gelbert L, et al.  Germline mutations in the von Hippel-Lindau tumor suppressor gene are similar to von Hippel-Lindau aberrations in sporadic renal cell carcinoma. Am J Hum Genet . 1994;;55:1092-1102.
62 +
Shuin T, Kondo K, Torigoe S, et al.  Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor-suppressor gene in primary human renal cell carcinomas. Cancer Res . 1994;;54:2852-2855.
63 +
Crossey PA, Richards FM, Foster K, et al.  Identification of intragenic mutations in the von Hippel-Lindau disease tumor suppressor gene and correlation with disease phenotype. Hum Mol Genet . 1994;;3:1303-1308.
64 +
Foster K, Prowse A, van den Berg A, et al.  Somatic mutations of the von Hippel-Lindau disease tumour suppressor gene in nonfamilial clear cell renal carcinoma. Hum Mol Genet . In press.
65 +
Siden TS, Kumlien J, Drumheller T, et al.  Identification of human chromosome region 3p14.2-21.3-specific YAC clones using Alu-PCR products from a radiation hybrid. Somat Cell Mol Genet . 1994;;20: 137-142.
66 +
Herman JG, Latif F, Weng Y, et al.  Silencing of the VHL tumor suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci U S A . 1994;;91:9700-9704.
67 +
Kovacs G, Fuzesi L, Emanual A, Kung HF.  Cytogenetics of papillary renal cell tumors. Genes Chromosom Cancer . 1991;;3:249-255.
68 +
Kovacs G.  Papillary renal cell carcinoma: a morphologic and cytogenetic study of 11 cases. Am J Pathol . 1989;;134:27-34.
69 +
Anglard P, Trahan E, Liu S, et al.  Molecular and cellular characterization of human renal cell carcinoma cell lines. Cancer Res . 1992;;52:348-356.
70 +
Zhuang Z, Gnarra J, Zbar B, Linehan WM, Lubensky IA.  Detection of the von Hippel-Lindau disease gene mutation by PCR and SSCP in sporadic renal cell carcinoma in paraffin-embedded tissue.  In: Modern Pathology, VII (abstracts from the annual meeting of the United States and Canadian Academy of Pathology); March 12-19, 1994;; San Francisco, Calif. Abstract 86A.
71 +
Liotta LA, Kleinerman J, Seidel GM.  Quantitative relationships of intravascular tumor cells, tumor vessels and pulmonary metastasis following tumor implantation. Cancer Res . 1974;;34:997-1004.
72 +
Buttler TP, Gullino PM.  Quantitation of cell shedding into efferent blood of mammary adenocarcinoma. Cancer Res . 1975;;35:512-515.
73 +
Pontes JE, Pescatori E, Connelly R, Hashimura T, Tubbs R.  Circulating cancer cells in renal-cell carcinoma. Prog Clin Biol Res . 1990;;348:1-12.
74 +
Sidransky D, Von Eschenbach A, Tsai YC, et al.  Identification of p53 gene mutations in bladder cancers and urine samples. Science . 1991;;252:706-709.
75 +
Selli C, Hinshaw WM, Woodard BH, Paulson DF.  Stratification of risk factors in renal cell carcinoma. Cancer . 1983;;52:899-903.
76 +
Bassil B, Dosoretz DE, Prout GR.  Validation of the tumor, nodes and metastasis classification of renal cell carcinoma. J Urol . 1985;;134:450-454.

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Interactive Graphics

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Boring CC, Squires TS, Tong T.  Cancer statistics. CA Cancer J Clin . 1994;;44:7-26.
2 +
Linehan WM, Shipley W, Parkinson D.  Cancer of the kidney and ureter.  In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practices of Oncology . Philadelphia, Pa: JB Lippincott Co; 1993;:1023-1051.
3 +
Reiter R, Zbar B, Linehan WM.  Molecular genetic studies of renal cell carcinoma: potential biologic and clinical significance for genitourinary malignancy.  In: Walsh PC, Retik AB, Vaughan ED, Stamey TA, eds. Campbell's Urology: Update 7 . Philadelphia, Pa: WB Saunders; 1993;:1-15.
4 +
Malker HR, Malker BK, McLaughlin JK, Blot WJ.  Kidney cancer among leather workers. Lancet . 1984;;1:56-57.
5 +
Maclure M.  Asbestos and renal adenocarcinoma: a case-control study. Environ Res . 1987;;42:353-361.
6 +
La Vecchia C, Negri E, D'Avanzo B, Franceschi S.  Smoking and renal cell carcinoma. Cancer Res . 1990;;50:5231-5233.
7 +
Yu MC, Mack TM, Hanisch R, Cicioni C, Henderson BE.  Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma. J Nati Cancer Inst . 1986;;77:351-356.
8 +
Chung-Park M, Parveen T, Lam M.  Acquired cystic disease of the kidneys and renal cell carcinoma in chronic renal insufficiency without dialysis treatment. Nephron . 1989;;53:157-161.
9 +
Matson MA, Cohen EP.  Acquired cystic kidney disease: occurrence, prevalence, and renal cancers. Medicine (Baltimore) . 1990;;69:217-226.
10 +
Brennan JF, Stilmant MM, Babayan RK, Siroky MB.  Acquired renal cystic disease: implications for the urologist. Br J Urol . 1991;;67:342-348.
11 +
Kovacs G, Ishikawa I.  High incidence of papillary renal cell tumours in patients on chronic haemodialysis. Histopathology . 1993;;22:135-139.
12 +
Bard RH, Lord B, Fromowitz F.  Papillary adenocarcinoma of kidney. Urology . 1982;;19:16-20.
13 +
Mellemgaard A, Engholm G, McLaughlin JK, Olsen JH.  Risk factors for renal cell carcinoma in Denmark, I: role of socioeconomic status, tobacco use, beverages, and family history. Cancer Causes Control . 1994;;5:105-113.
14 +
Harris H, Miller OJ, Klein G, Worst P, Tachibana T.  Suppression of malignancy by cell fusion. Nature . 1969;;223:363-368.
15 +
Stanbridge EJ.  Suppression of malignancy in human cells. Nature . 1976;;260:17-20.
16 +
Knudson AG Jr.  Antioncogenes and human cancer. Proc Natl Acad Sci U S A . 1993;;90:10914-10921.
17 +
Comings DE.  A general theory of carcinogenesis. Proc Natl Acad Sci U S A . 1973;;70:3324-3328.
18 +
Knudson AG Jr.  Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A . 1971;;68:820-823.
19 +
Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GAP.  Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature . 1990;;343:774-778.
20 +
Cavenee WK, Hansen MF, Nordenskjold M, et al.  Genetic origin of mutations predisposing to retinoblastoma. Science . 1985;;228:501-503.
21 +
Fung Y-KT, Murphree AL, T'Ang A, Quin J, Hinrichs SH, Benedict WF.  Structural evidence for the authenticity of the human retinoblastoma gene. Science . 1987;;236:1657-1661.
22 +
Xu G, O'Connell P, Viskochil D, et al.  The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell . 1990;;62:599-608.
23 +
Kinzler KW, Vogelstein B.  A gene for neurofibromatosis 2. Nature . 1993;;363:495.
24 +
Cohen AJ, Li FP, Berg S, et al.  Hereditary renal-cell carcinoma associated with a chromosomal translocation. N Engl J Med . 1979;;301:592-595.
25 +
Kovacs G, Brusa P, de Riese W.  Tissue-specific expression of a constitutional 3;6 translocation: development of multiple bilateral renal-cell carcinomas. Int J Cancer . 1989;;43:422-427.
26 +
Glenn GM, Choyke PL, Zbar B, Linehan WM.  Von Hippel-Lindau disease: clinical review and molecular genetics.  In: Anderson EE, ed: Problems in Urologic Surgery: Benign and Malignant Tumors of the Kidney . Philadelphia, Pa: JB Lippincott Co; 1990;:312-330.
27 +
Melmon KL, Rosen SW.  Lindau's disease: review of the literature and study of a large kindred. Am J Med . 1964;;36:595-617.
28 +
Zbar B, Tory K, Merino M, et al.  Hereditary papillary renal cell carcinoma. J Urol . 1994;;151: 561-566.
29 +
Zbar B, Glenn G, Lubensky I, et al.  Hereditary papillary renal cell carcinoma: clinical studies in 10 families. J Urol . In press.
30 +
Pathak S, Strong LC, Ferrell RE, Trindade A.  Familial renal cell carcinoma with a 3:11 chromosome translocation limited to tumor cells. Science . 1982;;217:939-941.
31 +
Zbar B.  Chromosomal deletions in lung cancer and renal cancer.  In: DeVita VT, Hellman S, Rosenberg SA, eds. Important Advances in Oncology 1989 . Philadelphia, Pa: JB Lippincott Co; 1989;:41-60.
32 +
Yoshida HA, Ohyashiki K, Ochi H, et al.  Cytogenetic studies of tumor tissue from patients with nonfamilial renal cell carcinoma. Cancer Res . 1986;; 46:2139-2147.
33 +
de Jong B, Oosterhuis JW, Idenburg VJ, Castedo SM, Dam A, Mensink HJ.  Cytogenetics of 12 cases of renal adenocarcinoma. Cancer Genet Cytogenet . 1988;;30:53-61.
34 +
Presti JC, Rao PH, Chen Q, et al.  Histopathological, cytogenetic, and molecular characterization of renal cortical tumors. Cancer Res . 1991;;51:1544-1552.
35 +
Zbar B, Brauch H, Talmadge C, Linehan M.  Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. Nature . 1987;;327: 721-724.
36 +
Kovacs G, Erlandsson R, Boldog F, et al.  Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc Natl Acad Sci US A . 1988;;85:1571-1575.
37 +
Kovacs G, Wilkens L, Papp T, de Riese W.  Differentiation between papillary and nonpapillary renal cell carcinomas by DNA analysis. J Natl Cancer Inst . 1989;;81:527-530.
38 +
Anglard P, Brauch TH, Weiss GH, et al.  Molecular analysis of genetic changes in the origin and development of renal cell carcinoma. Cancer Res . 1991;;51:1071-1077.
39 +
Boldog F, Arheden K, Imreh S, et al.  Involvement of 3p deletions in sporadic and hereditary forms of renal cell carcinoma. Genes Chromosom Cancer . 1991;;3:403-406.
40 +
Morita R, Ishikawa J, Tsutsumi M, et al.  Allelotype of renal cell carcinoma. Cancer Res . 1991;; 51:820-823.
41 +
Ogawa O, Kakehi Y, Ogawa K, Koshiba M, Sugiyama T, Yoshida O.  Allelic loss at chromosome 3p characterizes clear cell phenotype of renal cell carcinoma. Cancer Res . 1991;;51:949-953.
42 +
Yamakawa K, Morita R, Takahashi E, Hori T, Ishikawa J, Nakamura Y.  A detailed deletion mapping of the short arm of chromosome 3 in sporadic renal cell carcinoma. Cancer Res . 1991;;51:4707-4711.
43 +
Szucs S, Muller-Brechlin R, DeRiese W, Kovacs G.  Deletion 3p: the only chromosome loss in a primary renal cell carcinoma. Cancer Genet Cytogenet . 1987;;26:369-373.
44 +
Kovacs G, Frisch S.  Clonal chromosome abnormalities in tumor cells from patients with sporadic renal cell carcinomas. Cancer Res . 1989;;49:651-659.
45 +
Carroll PR, Murty VVS, Reuter V, et al.  Abnormalities of chromosome region 3p12-14 characterize clear cell renal carcinoma. Cancer Genet Cytogenet . 1987;;26:253-259.
46 +
Brooks JD, Bova GS, Marshall FF, Isaacs WB.  Tumor suppressor gene allelic loss in human renal cancers. J Urol . 1993;;150:1278-1283.
47 +
van der Hout AH, van den Berg E, van den Vlies P, et al.  Loss of heterozygosity at the short arm of chromosome 3 in renal-cell cancer correlates with the cytological tumour type. Int J Cancer . 1993;;53:353-357.
48 +
Linehan WM, et al.  Genetic basis of renal cell cancer.  In: DeVita VT, Hellman S, Rosenberg SA, eds. Important Advances in Oncology, 1993 . Philadelphia, Pa: JB Lippincott Co; 1993;:47-70.
49 +
Maher ER, Iselius L, Yates JR, et al.  Von Hippel-Lindau disease: a genetic study. J Med Genet . 1991;;28:443-447.
50 +
Poston CD, Jaffe GS, Solomon D, Zbar B, Linehan WM, Walther MM.  Characterization of the renal pathology of a familial form of renal cell carcinoma associated with von Hippel-Lindau disease: clinical and molecular genetic implications. J Urol . In press.
51 +
Tory K, Brauch H, Linehan M, et al.  Specific genetic change in tumors associated with von Hippel-Lindau disease. J Natl Cancer Inst . 1989;;81:1097-1101.
52 +
Seizinger BR, Rouleau GA, Ozelius LJ, et al.  Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature . 1988;;332:268-269.
53 +
Lerman MI, Latif F, Glenn GM, et al.  Isolation and regional localization of a large collection (2,000) of single copy DNA fragments on human chromosome 3 for mapping and cloning tumor suppressor genes. Hum Genet . 1991;;86:567-577.
54 +
Hosoe S, Brauch H, Latif F, et al.  Localization of the von Hippel-Lindau disease gene to a small region of chromosome 3. Genomics . 1990;;8:634-640.
55 +
Glenn GM, Daniel LN, Choyke P, et al.  Von Hippel-Lindau disease: distinct phenotypes suggest more than one mutant allele at the VHL locus. Hum Genet . 1991;;87:207-210.
56 +
Glenn GM, Linehan WM, Hosoe S, et al.  Screening for von Hippel-Lindau disease by DNA-polymorphism analysis. JAMA . 1992;;267:1226-1231.
57 +
Gnarra JR, Tory K, Weng Y, et al.  Mutation of the VHL tumour suppressor gene in renal carcinoma. Nat Genet . 1994;;7:85-90.
58 +
Yao M, Latif F, Kuzmin I, et al.  Von Hippel-Lindau disease: identification of deletion mutations by pulsed field gel electrophoresis. Hum Genet . 1993;;92:605-614.
59 +
Latif F, Tory K, Gnarra J, et al.  Identification of the von Hippel-Lindau disease tumor suppressor gene. Science . 1993;;260:1317-1320.
60 +
Chen F, Kishida T, Yao M, et al.  Germ-line mutations in the von Hippel-Lindau disease tumor suppressor gene: correlation with phenotype. Hum Mutat . In press.
61 +
Whaley JM, Naglich J, Gelbert L, et al.  Germline mutations in the von Hippel-Lindau tumor suppressor gene are similar to von Hippel-Lindau aberrations in sporadic renal cell carcinoma. Am J Hum Genet . 1994;;55:1092-1102.
62 +
Shuin T, Kondo K, Torigoe S, et al.  Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor-suppressor gene in primary human renal cell carcinomas. Cancer Res . 1994;;54:2852-2855.
63 +
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To understand the clinical management of acute heart failure syndromes.
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Compression-Only CPR: Pushing the Science Forward
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AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
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