Major role for a 3p21 region and lack of involvement of the t(3;8) breakpoint region in the development of renal cell carcinoma suggested by loss of heterozygosity analysis

Berg, Anke van den; Hulsbeek, Miriam; DeJong, D. W.; Kok, Klaas; Veldhuis, Pmjf; Roche, Joëlle; Buys, Chcm

doi:10.1002/(sici)1098-2264(199601)15:1<64::aid-gcc9>3.0.co;2-2

Cited by 52 publications

(17 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The LOH frequency for various markers varied from 15 to 45% [20] and from 16 to 41% in this work; 26% and 29%, respectively, for the common D3S1286 marker. Our results are in good agreement with the data [13,15,16], showing a considerable contribution of discontinuous multiple deletions in the development of RCC.…”

Section: Discussionsupporting

confidence: 92%

Comparative allelotyping epithelial tumors of the short arm of human chromosome 3 in of four different types

Брага¹,

Pugacheva²,

Bazov³

et al. 1999

FEBS Letters

View full text Add to dashboard Cite

Comparative allelotyping of the short arm of human chromosome 3 (3p) in four types of epithelial carcinomas was performed using an identical set of polymorphic markers. In total, 117 samples of non-papillary renal cell carcinoma (RCC), non-small cell lung carcinoma (NSCLC), carcinoma of uterine cervix (CC), and breast carcinoma (BC) were screened for loss of heterozygosity (LOH) with 10 di-, tri-and tetrameric markers covering nine bands of 3p. High LOH frequencies were detected in at least one locus: RCC (36143, 84%), BC (20/26, 77%), NSCLC (16124, 67%), and CC (15124, 62%). Small interstitial deletions prevailed in BC and CC whereas large continuous and discontinuous deletions were mainly found in RCC and NSCLC. Different epithelial tumors displayed unique LOH profiles with partial overlaps in 3p26.1, 3p21.31, and 3p13. The overlap around D3S2409 (3p21.31) appeared common for RCC, BC and CC.

show abstract

Section: Discussionsupporting

confidence: 92%

Comparative allelotyping epithelial tumors of the short arm of human chromosome 3 in of four different types

Брага¹,

Pugacheva²,

Bazov³

et al. 1999

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…When multiple LOH are present, tumors with LOH on 3p21-p22 also carry LOH on 3p14 or 3p25 (5,16,17), suggesting that LOH on 3p21-p22 is an important event in RCC progression. However, another study of multiple tumors from a single patient established that early 3p allelic losses (adenoma but not carcinoma-related) occurred predominantly in the 3p25 or the 3p12-p14 regions, but not in 3p21-3p22 (29).…”

Section: Discussionmentioning

confidence: 99%

“…Although the overall frequency of the specific LOH is not high, chromosome transfer experiments indicated that the 3p12-p14 region could suppress the tumorigenic properties of some clear RCC cell lines (14), implying the presence of a gene or genes involved in the origin and͞or development of clear RCC. This role may be attributed to the FHIT gene at 3p14.3 (15), and͞or other tumor-suppressor genes (TSGs) residing in 3p12.Multiple studies have identified LOH on 3p21-p22 as the most frequent 3p loss in renal tumor development (4,5,16,17). Recent data indicate that this region consists of two distinct subregions: centromeric 3p21.3 and telomeric 3p21.3-p22, with both regions being deleted frequently (5).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The candidate tumor suppressor gene, RASSF1A , from human chromosome 3p21.3 is involved in kidney tumorigenesis

Dreijerink

Брага

Kuzmin

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

276

218

View full text Add to dashboard Cite

Clear cell-type renal cell carcinomas (clear RCC) are characterized almost universally by loss of heterozygosity on chromosome 3p, which usually involves any combination of three regions: 3p25-p26 (harboring the VHL gene), 3p12-p14.2 (containing the FHIT gene), and 3p21-p22, implying inactivation of the resident tumorsuppressor genes (TSGs). For the 3p21-p22 region, the affected TSGs remain, at present, unknown. Recently, the RAS association family 1 gene (isoform RASSF1A), located at 3p21.3, has been identified as a candidate lung and breast TSG. In this report, we demonstrate aberrant silencing by hypermethylation of RASSF1A in both VHL-caused clear RCC tumors and clear RCC without VHL inactivation. We found hypermethylation of RASSF1A's GC-rich putative promoter region in most of analyzed samples, including 39 of 43 primary tumors (91%). The promoter was methylated partially or completely in all 18 RCC cell lines analyzed. Methylation of the GC-rich putative RASSF1A promoter region and loss of transcription of the corresponding mRNA were related causally. RASSF1A expression was reactivated after treatment with 5-aza-2 -deoxycytidine. Forced expression of RASSF1A transcripts in KRC͞Y, a renal carcinoma cell line containing a normal and expressed VHL gene, suppressed growth on plastic dishes and anchorage-independent colony formation in soft agar. Mutant RASSF1A had reduced growth suppression activity significantly. These data suggest that RASSF1A is the candidate renal TSG gene for the 3p21.3 region. L oss of heterozygosity (LOH) of chromosome 3p is the most common event in clear cell-type renal cell carcinomas (clear RCC). It involves one or more of the three major commonly deleted regions (1-3) that may be subdivided further by using pioneering stringent criteria for LOH analysis (4-6).The most frequent form of hereditary RCC is the familial VHL cancer syndrome (7). The VHL gene was mapped to 3p25 and was isolated by positional cloning (8). It was inactivated by intragenic and genomic deletions and various kinds of mutations in 100% of analyzed VHL families and in a large portion of sporadic clear RCC (9). Inactivation of VHL by promoter hypermethylation (10) in sporadic clear RCC was noted also and was observed quite frequently (20%). However, in other sporadic clear RCC (reaching in some studies 30-50%) and some non-VHL clear RCC families (11, 12), VHL was not affected (see review in ref. 13).Another commonly deleted region was found at 3p12-p14. Although the overall frequency of the specific LOH is not high, chromosome transfer experiments indicated that the 3p12-p14 region could suppress the tumorigenic properties of some clear RCC cell lines (14), implying the presence of a gene or genes involved in the origin and͞or development of clear RCC. This role may be attributed to the FHIT gene at 3p14.3 (15), and͞or other tumor-suppressor genes (TSGs) residing in 3p12.Multiple studies have identified LOH on 3p21-p22 as the most frequent 3p loss in renal tumor development (4,5,16,17). Recent data indicate that ...

show abstract

“…However, it is likely that other clear cell renal cell carcinoma gatekeeper genes remain to be identified. 14 18 Thus, a considerable proportion of sporadic clear cell renal cell carcinomas do not have evidence of VHL inactivation and hereditary clear cell carcinoma kindreds are not allelic with VHL disease. In a previous smaller study, we identified frequent chromosome 3p allele loss in sporadic clear cell renal cell carcinoma, with and without VHL inactivation, suggesting that additional non-VHL chromosome 3p tumour suppressor genes play a crucial role in the pathogenesis of clear cell renal cell carcinoma.…”

mentioning

confidence: 99%

Role of chromosome 3p12-p21 tumour suppressor genes in clear cell renal cell carcinoma: analysis of VHL dependent and VHL independent pathways of tumorigenesis

Martínez

Fullwood²,

Kondo³

et al. 2000

Molecular Pathology

View full text Add to dashboard Cite

Renal cell carcinoma accounts for approximately 2% of adult malignancies and is the most common adult kidney neoplasm. Renal cell carcinoma is histopathologically heterogeneous, most sporadic renal cell carcinomas (about 80%) are classified as clear cell (or nonpapillary) tumours, with non-clear cell tumours predominantly classed as chromophilic (12%) or chromophobe (5%). Cytogenetic and molecular genetic studies in the 1980s identified chromosome 3p deletions as the most common genetic event in renal cell carcinoma, [1][2][3] and subsequently the VHL tumour suppressor gene was mapped to chromosome 3p25. [4][5][6] Germline mutations of the VHL tumour suppressor gene cause von Hippel-Lindau (VHL) disease and are associated with a high risk of early onset and multicentric clear cell renal cell carcinoma. 7-9Somatic VHL gene mutations are found in 43-57% of clear cell renal cell carcinoma cell lines and primary tumours, 10 11 and an additional 11-19% of renal cell carcinoma cell lines and primary tumours demonstrate promoter hypermethylation and transcriptional silencing of the VHL gene.12-14 VHL gene inactivation is not a feature of non-clear cell renal cell carcinoma, and recently germline and somatic mutations in the MET protooncogene have been reported in familial and sporadic nonclear cell papillary renal cell carcinoma. 16The reintroduction of wild-type VHL into VHL null clear cell renal cell carcinoma cell lines suppresses tumorigenicity in vivo.17 These studies clearly implicate inactivation of VHL in the pathogenesis of many clear cell renal cell carcinomas and establish VHL as a crucial gatekeeper for the most common form of kidney cancer. However, it is likely that other clear cell renal cell carcinoma gatekeeper genes remain to be identified.14 18 Thus, a considerable proportion of sporadic clear cell renal cell carcinomas do not have evidence of VHL inactivation and hereditary clear cell carcinoma kindreds are not allelic with VHL disease. In a previous smaller study, we identified frequent chromosome 3p allele loss in sporadic clear cell renal cell carcinoma, with and without VHL inactivation, suggesting that additional non-VHL chromosome 3p tumour suppressor

show abstract

Major role for a 3p21 region and lack of involvement of the t(3;8) breakpoint region in the development of renal cell carcinoma suggested by loss of heterozygosity analysis

Cited by 52 publications

References 23 publications

Comparative allelotyping epithelial tumors of the short arm of human chromosome 3 in of four different types

Comparative allelotyping epithelial tumors of the short arm of human chromosome 3 in of four different types

The candidate tumor suppressor gene, RASSF1A , from human chromosome 3p21.3 is involved in kidney tumorigenesis

Role of chromosome 3p12-p21 tumour suppressor genes in clear cell renal cell carcinoma: analysis of VHL dependent and VHL independent pathways of tumorigenesis

Contact Info

Product

Resources

About