Genetics as a diagnostic tool in sarcomatoid renal-cell cancer

Dijkhuizen, Trijnie; Vandenberg, E; Berg, A. van den; Vandeveen, Ay; Faber, Hette; Buys, Chcm; Störkel, Stephan; Dejong, B; Dam, Anke

doi:10.1002/(sici)1097-0215(19970717)72:2<265::aid-ijc11>3.0.co;2-f

Cited by 21 publications

(7 citation statements)

References 13 publications

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“…51 The genetic abnormalities associated with the evolution of a spindle-cell morphology are poorly understood, although losses of chromosome 4q, 6q, 8p, 9, 13q, 14 and 17p, and gains of chromosome 5, 12, and 20 have been noted. 54,55 In a separate study gains of chromosome 1, 2, 6, 10, and 17 have been demonstrated for chromophobe sarcomatoid carcinoma. 56 There is also evidence to indicate that carcinomas evolve into sarcomatoid carcinomas through a variety of mutational steps as collagen expression of carcinomas showing early spindle-cell change differs from that of well-developed sarcomatoid carcinomas.…”

Section: Sarcomatoid and Rhabdoid Differentiationmentioning

confidence: 90%

Advances and controversies in grading and staging of renal cell carcinoma

2009

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Despite the considerable progress made in our understanding of the pathogenesis, genetics, and pathology of renal cell carcinoma (RCC), difficulties remain relating to the prediction of clinical outcome for individual cases. Although there is evidence to show that high-grade tumors have a poorer prognosis when compared to those of low grade, debate remains regarding the predictive value of grading, especially for those tumors classified into the intermediate grades. Numerous composite morphologic and nuclear grading systems have been proposed for RCC and although that of the Fuhrman classification have achieved widespread usage, the validity of the grading criteria of this classification has been questioned. In addition, there are few studies that have attempted to validate the Fuhrman system for RCCs beyond that of the clear cell subtype. Recent studies have indicated that grading of papillary RCC should be based on nucleolar prominence alone and that the components of the Fuhrman grading classification do not provide prognostic information for chromophobe RCC. Independent of tumor grade, the prognostic importance of tumor stage for RCC is well recognized. The Union Internationale Contre le Cancer/American Joint Committee for Cancer Staging and End Results Reporting TNM staging system is now in its sixth edition (2002) and recent refinements have focused on defining size cut points that will identify apparently localized tumors that will develop recurrence and/or metastases despite attempted curative surgery. In parallel with these studies it has been shown that infiltration of the renal sinus is an important prognostic factor, being observed in almost all tumors 47 cm in diameter. Questions remain as to the appropriate stratification of regional extension of RCC, as defined in the T3 tumor-staging category. Recent modifications to this category have been suggested combining the level of infiltration of the venous outflow tract with the presence or absence of infiltration of the adrenal gland and/or perirenal fat. Similarly, the utility of classifying lymph node involvement by tumor is debated, although it is well recognized that lymph node infiltration is associated with a poor prognosis. Although the current TNM classification does provide useful prognostic information it would appear that further modifications are justified to enhance the predictive value of staging for RCC.

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Section: Sarcomatoid and Rhabdoid Differentiationmentioning

confidence: 90%

Advances and controversies in grading and staging of renal cell carcinoma

2009

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“…Loss of heterozygosity at 3p25, gains of chromosomes 7 and 10, and an isochromosome 17q are among the few cytogenetic aberrations identified in early, low-stage sporadic clear cell renal cell carcinomas (RCCs) (Anglard et al, 1991;Dijkhuizen et al, 1997;Elfving et al, 1997;Wada et al, 1997). Advanced RCCs are characterized by hyperdiploidy or marked aneuploidy, with chromosomal aberrations involving all autosomes and with nonrandom changes most commonly mapped to 1p, 2q, 3p, 5q, 6q, and 8p (Mitelman, 1994;Presti et al, 1996;www.ncbi.nlm.mitelmansum.cgi).…”

Section: Introductionmentioning

confidence: 99%

Molecular cytogenetic characterization of early and late renal cell carcinomas in Von Hippel‐Lindau disease

Phillips

Ghadimi

Wangsa

et al. 2001

Genes Chromosomes & Cancer

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Deletions of 3p25, gains of chromosomes 7 and 10, and isochromosome 17q are known cytogenetic aberrations in sporadic renal cell carcinoma (RCC). In addition, a majority of RCCs have loss of heterozygosity (LOH) of the Von Hippel-Lindau (VHL) gene located at chromosome band 3p25. Patients who inherit a germline mutation of the VHL gene can develop multifocal RCCs and other solid tumors, including malignancies of the pancreas, adrenal medulla, and brain. VHL tumors follow the two-hit model of tumorigenesis, as LOH of VHL, a classic tumor suppressor gene, is the critical event in the development of the neoplastic phenotype. In an attempt to define the cytogenetic aberrations from early tumors to late RCC further, we applied spectral karyotyping (SKY) to 23 renal tumors harvested from 6 unrelated VHL patients undergoing surgery. Cysts and low-grade solid lesions were near-diploid and contained 1-2 reciprocal translocations, dicentric chromosomes, and/or isochromosomes. A variety of sole numerical aberrations included gains of chromosomes 1, 2, 4, 7, 10, 13, 21, and the X chromosome, although no tumors had sole numerical losses. Three patients shared a breakpoint at 2p21-22, and three others shared a dicentric chromosome 9 or an isochromosome 9q. In contrast to the near-diploidy of the low-grade lesions, a high-grade lesion and its nodal metastasis were markedly aneuploid, revealed loss of VHL by fluorescence in situ hybridization (FISH), and contained recurrent unbalanced translocations and losses of chromosome arms 2q, 3p, 4q, 9p, 14q, and 19p as demonstrated by comparative genomic hybridization (CGH). By combining SKY, CGH, and FISH of multiple tumors from the same VHL kidney, we have begun to identify chromosomal aberrations in the earliest stages of VHL-related renal cell tumors. Our current findings illustrate the cytogenetic heterogeneity of different VHL lesions from the same kidney, which supports the multiclonal origins of hereditary RCCs. Published 2001 Wiley-Liss, Inc.

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“…Within this group, a subset is encountered with chromosomal translocations involving the Xp11region, mostly a (X;1)(p11;q21) translocation. There is accumulating evidence that these tumors de®ne a distinct subgroup of renal cell cancers with a relatively early age of onset and a lower male-female preponderance as compared to other renal cell cancers (Tonk et al, 1995;Dijkhuizen et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Nuclear localization and transactivating capacities of the papillary renal cell carcinoma-associated TFE3 and PRCC (fusion) proteins

et al. 2000

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The papillary renal cell carcinoma-associated t(X;1)(p11;q21) leads to fusion of the transcription factor TFE3 gene on the X-chromosome to a novel gene, PRCC, on chromosome 1. As a result, two putative fusion proteins are formed: PRCCTFE3, which contains all known domains for DNA binding, dimerization, and transactivation of the TFE3 protein, and the reciprocal product TFE3PRCC. Upon transfection into COS cells, both wild type and fusion proteins were found to be located in the nucleus. When comparing the transactivating capacities of these (fusion) proteins, signi®cant dierences were noted. PRCCTFE3 acted as a threefold better transactivator than wild type TFE3 both in a TFE3-speci®c and in a general (Zebra) reporter assay. In addition, PRCC and the two fusion proteins were found to be potent transactivators in the Zebra reporter assay. We propose that, as a result of the (X;1) translocation, fusion of the N-terminal PRCC sequences to TFE3 alters the transactivation capacity of the transcription factor thus leading to aberrant gene regulation and, ultimately, tumor formation. Oncogene (2000) 19, 69 ± 74.

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Genetics as a diagnostic tool in sarcomatoid renal-cell cancer

Cited by 21 publications

References 13 publications

Advances and controversies in grading and staging of renal cell carcinoma

Advances and controversies in grading and staging of renal cell carcinoma

Molecular cytogenetic characterization of early and late renal cell carcinomas in Von Hippel‐Lindau disease

Nuclear localization and transactivating capacities of the papillary renal cell carcinoma-associated TFE3 and PRCC (fusion) proteins

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