VHL, the story of a tumour suppressor gene

被引：588

作者：

Gossage, Lucy ^{[1
,2
,3
]}

Eisen, Tim ^{[1
,2
]}

Maher, Eamonn R. ^{[1
,4
,5
]}

机构：

[1] Cambridge Univ Hosp NHS Fdn Trust, Cambridge CB2 0QQ, England

[2] Univ Cambridge, Dept Oncol, Cambridge CB2 0QQ, England

[3] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England

[4] Univ Cambridge, Dept Med Genet, Cambridge CB2 0QQ, England

[5] NIHR Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England

来源：

NATURE REVIEWS CANCER | 2015年 / 15卷 / 01期

基金：

欧洲研究理事会;

关键词：

RENAL-CELL-CARCINOMA; HYPOXIA-INDUCIBLE-FACTOR; HIPPEL-LINDAU-DISEASE; ENDOTHELIAL GROWTH-FACTOR; GENOTYPE-PHENOTYPE CORRELATIONS; BIOLOGICALLY-ACTIVE PRODUCT; GERM-LINE MUTATIONS; RNA-POLYMERASE-II; HIF-ALPHA; MESSENGER-RNA;

D O I：

10.1038/nrc3844

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Since the Von Hippel-Lindau (VHL) disease tumour suppressor gene VHL was identified in 1993 as the genetic basis for a rare disorder, it has proved to be of wide medical and scientific interest. VHL tumour suppressor protein (pVHL) plays a key part in cellular oxygen sensing by targeting hypoxia-inducible factors for ubiquitylation and proteasomal degradation. Early inactivation of VHL is commonly seen in clear-cell renal cell carcinoma (ccRCC), and insights gained from the functional analysis of pVHL have provided the foundation for the routine treatment of advanced-stage ccRCC with novel targeted therapies. However, recent sequencing studies have identified additional driver genes that are involved in the pathogenesis of ccRCC. As our understanding of the importance of VHL matures, it is timely to review progress from its initial description to current knowledge of VHL biology, as well as future prospects for novel medical treatments for VHL disease and ccRCC.

引用

页码：55 / 64

页数：10

共 221 条

[21] GERMLINE MUTATIONS IN THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE - CORRELATIONS WITH PHENOTYPE [J].

CHEN, F ;

KISHIDA, T ;

YAO, M ;

HUSTAD, T ;

GLAVAC, D ;

DEAN, M ;

GNARRA, JR ;

ORCUTT, ML ;

DUH, FM ;

GLENN, G ;

GREEN, J ;

HSIA, YE ;

LAMIELL, J ;

LI, H ;

WEI, MH ;

SCHMIDT, L ;

TORY, K ;

KUZMIN, I ;

STACKHOUSE, T ;

LATIF, F ;

LINEHAN, WM ;

LERMAN, M ;

ZBAR, B .

HUMAN MUTATION, 1995, 5 (01) :66-75

[22] Potential histologic and molecular predictors of response to temsirolimus in patients with advanced renal cell carcinoma [J].

Cho, Daniel ;

Signoretti, Sabina ;

Dabora, Sandra ;

Regan, Meredith ;

Seeley, Apryle ;

Mariotti, Mauro ;

Youmans, Amanda ;

Polivy, Adam ;

Mandato, Lucy ;

McDermott, David ;

Stanbridge, Eric ;

Atkins, Michael .

CLINICAL GENITOURINARY CANCER, 2007, 5 (06) :379-385

[23] von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma [J].

Choueiri, Toni K. ;

Vaziri, Susan A. J. ;

Jaeger, Erich ;

Elson, Paul ;

Wood, Laura ;

Bhalla, Ish Prasad ;

Small, Eric J. ;

Weinberg, Vivian ;

Sein, Nancy ;

Simko, Jeff ;

Golshayan, Ali-Reza ;

Sercia, Linda ;

Zhou, Ming ;

Waldman, Frederic M. ;

Rini, Brian I. ;

Bukowski, Ronald M. ;

Ganapathi, Ram .

JOURNAL OF UROLOGY, 2008, 180 (03) :860-865

[24] The Role of Aberrant VHL/HIF Pathway Elements in Predicting Clinical Outcome to Pazopanib Therapy in Patients with Metastatic Clear-Cell Renal Cell Carcinoma [J].

Choueiri, Toni K. ;

Fay, Andre P. ;

Gagnon, Robert ;

Lin, Ying ;

Bahamon, Brittany ;

Brown, Victoria ;

Rosenberg, Jonathan E. ;

Hutson, Thomas E. ;

Baker-Neblett, Katherine L. ;

Carpenter, Christopher ;

Liu, Yuan ;

Pandite, Lini ;

Signoretti, Sabina .

CLINICAL CANCER RESEARCH, 2013, 19 (18) :5218-5226

[25]

Clifford SC, 1998, GENE CHROMOSOME CANC, V22, P200, DOI 10.1002/(SICI)1098-2264(199807)22:3<200::AID-GCC5>3.0.CO

[26]

2-#

[27] Contrasting effects on HIF-1α regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease [J].

Clifford, SC ;

Cockman, ME ;

Smallwood, AC ;

Mole, DR ;

Woodward, ER ;

Maxwell, PH ;

Ratcliffe, PJ ;

Maher, ER .

HUMAN MOLECULAR GENETICS, 2001, 10 (10) :1029-1038

[28] Hypoxia inducible factor-α binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein [J].

Cockman, ME ;

Masson, N ;

Mole, DR ;

Jaakkola, P ;

Chang, GW ;

Clifford, SC ;

Maher, ER ;

Pugh, CW ;

Ratcliffe, PJ ;

Maxwell, PH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (33) :25733-25741

[29] An important von Hippel-Lindau tumor suppressor domain mediates Sp1-binding and self-association [J].

Cohen, HT ;

Zhou, M ;

Welsh, AM ;

Zarghamee, S ;

Scholz, H ;

Mukhopadhyay, D ;

Kishida, T ;

Zbar, B ;

Knebelmann, B ;

Sukhatme, VP .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 266 (01) :43-50

[30]

Collins E., 1894, Trans Ophthalmol Soc UK, V14, P141

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