Allele loss in Wilms tumors of chromosome arms 11q, 16q, and 22q correlates with clinicopathological parameters

Klamt, B; Schulze, Michael; Thäte, Claudia; Mareš, Jaroslav; Goetz, Peter G.; Kodet, Roman; Scheurlen, Wolfram; Weirich, A.; Graf, Norbert; Gessler, Manfred

doi:10.1002/(sici)1098-2264(199808)22:4<287::aid-gcc4>3.0.co;2-r

Cited by 75 publications

(63 citation statements)

References 29 publications

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“…In the latter group, a number of studies, including cytogenetics, loss of heterozygosity (LOH) and comparative genomic hybridization (CGH) analyses, have revealed the involvement of different chromosomal regions. These include 11p15-where a cluster of imprinted genes, among which H19 and IGF2, is mapped (Reeve et al, 1989;Ogawa et al, 1993;Rainier et al, 1993)-1p, 11q, 16q, 22q (Maw et al, 1992Grundy et al, 1994;Radice et al, 1995;Klamt et al, 1998;Hing et al, 2001;Hoglund et al, 2004;Ruteshouser et al, 2007) and 7p, where two candidate WT suppressor genes, PTH1 and POU6F2, have been identified (Vernon et al, 2003;Perotti et al, 2004).…”

Section: Introductionmentioning

confidence: 80%

Functional inactivation of the WTX gene is not a frequent event in Wilms’ tumors

et al. 2008

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Section: Introductionmentioning

confidence: 80%

Functional inactivation of the WTX gene is not a frequent event in Wilms’ tumors

et al. 2008

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“…No specific gene mutation has yet been identified as a direct contributor to their pathogenesis. Wilms tumor is known to have allelic loss at numerous loci (Grundy et al, , 1998Law et al, 1997;Klamt et al, 1998;Natrajan et al, 2006). One Wilms tumor gene (WT1) has been identified and mapped to 11p13 (Call et al, 1990;Gessler et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

et al. 2006

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Inactivation of the HRPT2 gene encoding parafibromin was recently linked to the familial hyperparathyroidismjaw tumor syndrome. Patients with this syndrome carry an increased risk of parathyroid and renal tumors. To determine the relevance of HRPT2 for sporadic renal tumors, clear cell, papillary and chromophobe renal cell carcinomas as well as oncocytomas and Wilms tumors were analysed for HRPT2 gene alterations. Loss of heterozygosity (LOH) of HRPT2 was found in seven of 56 (12.5%) clear cell, three of 14 (21%) papillary, six of 10 (60%) chromophobe renal cell carcinomas, three of eight (38%) oncocytomas and four of 10 (40%) Wilms tumors. In addition, two novel HRPT2 point mutations, causing K34Q and R292K changes in parafibromin, were detected in one clear cell carcinoma and one Wilms tumor, respectively. These tumors displayed LOH of the remaining wild-type allele, but interestingly no von HippelLindau (VHL) mutation. Functional analysis revealed that the K34Q mutant species of parafibromin is, unlike wild-type protein, defective in suppressing cyclin D1 expression in vivo. Taken together, these results suggest that renal cancer-associated mutations in parafibromin occur in the absence of VHL mutation, which in turn may contribute to constitutively elevated cyclin D1 expression and abnormal cell proliferation.

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“…Chromosome 16q allele loss occurs in up to 25% of Wilms' tumours and has been associated with a poorer prognosis (Austruy et al, 1995;Grundy et al, 1996Grundy et al, , 1998Klamt et al, 1998;Skotnicka-Klonowicz et al, 2000). Candidate 16q Wilms' tumour suppressor genes include CDH1 and CDH13 (H-cadherin, 16q24.2-3).…”

Section: Discussionmentioning

confidence: 99%

Multigene methylation analysis of Wilms' tumour and adult renal cell carcinoma

et al. 2003

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To investigate the role of epigenetic gene silencing in the pathogenesis of Wilms' tumour and renal cell carcinoma (RCC), we determined their methylation profile using a candidate gene approach. Thus, 40 Wilms' tumours and up to 49 adult RCC were analysed by methylation-specific PCR for promoter methylation at CASP8, CDH1, CDH13, DAPK, MGMT, NORE1A, p14 ARF and RARB2 in primary Wilms' tumours and CASP8, CDH1, CDH13, CRBP1, DAPK, MGMT, MT1G, NORE1A, p16 INK4a , SDHB and RARB2 in primary RCC. Both tumour sample sets had previously been analysed for RASSF1A promoter methylation, and p16 INK4a methylation results were also available for the Wilms' tumour samples. Wilms' tumours demonstrated a high incidence of methylation at CASP8 (43%) and MGMT (30%), intermediate frequencies at NORE1A (15%), p14 ARF (15%), p16 INK4a (10%), DAPK (11%) and CRBP1 (9%), but promoter methylation was rare or absent at RARB2 (0%), CDH13 (0%) and CDH1 (3%). No association was detected between methylation of RASSF1A, CASP8 or MGMT in individual tumours. The frequency of MGMT methylation was higher in stage 1 and 2 tumours (50%) than in stage 3 and 4 tumours (17%) but this did not reach statistical significance (P ¼ 0.06). RCC were most frequently methylated at DAPK (24%), MT1G (20%), NORE1A (19%), CDH1 (16%) and MGMT (9%) and not or rarely at SDHB (4%), RARB2 (0%), p16 INK4a (0%) and CDH13 (3%). There were no associations between methylation of RASSF1A, DAPK and CDH1 in individual tumours. Papillary RCC demonstrated a higher frequency of DAPK methylation (43%) than clear cell tumours (19%) (P ¼ 0.14). We have demonstrated that de novo promoter methylation is frequent in Wilms' tumour and RCC, and these data enable methylation profiles to be constructed for each tumour type. Thus, combining our results with data published previously, it appears that promoter methylation occurs frequently (X20% of primary tumours) at CASP8, SLIT2 and RASSF1A in Wilms' tumour and at RASSF1A, TIMP3, DAPK, SLIT2, MT1G and GSTP1 in RCC.

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Allele loss in Wilms tumors of chromosome arms 11q, 16q, and 22q correlates with clinicopathological parameters

Cited by 75 publications

References 29 publications

Functional inactivation of the WTX gene is not a frequent event in Wilms’ tumors

Functional inactivation of the WTX gene is not a frequent event in Wilms’ tumors

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

Multigene methylation analysis of Wilms' tumour and adult renal cell carcinoma

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