Genetic progression of renal cell carcinoma

Moch, Holger; Mihatsch, Michael J.

doi:10.1007/s00428-002-0685-y

Cited by 20 publications

(12 citation statements)

References 59 publications

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“…Among other histotypes various gains and losses of DNA sequence copy number have been found when comparing primary clear cell or papillary renal cell carcinomas and metastatic lesions. [39][40][41][42][43][44] The histochemical and immunohistochemical analyses showed results as expected, regarding the epithelial component. 23,45,46 Parvalbumin and CK7 showed immunoexpression in the chromophobic cells whereas vimentin was absent; Hale's colloidal iron stain was diffusely positive.…”

Section: Discussionmentioning

confidence: 61%

Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma

et al. 2007

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The hallmark of chromophobe renal cell carcinoma is multiple chromosomal losses from among chromosomes 1, 2, 6, 10 and 17. Chromophobe renal cell carcinoma with distant metastases or sarcomatoid transformation are uncommon and little is known about their chromosomal abnormalities. We collected six sarcomatoid chromophobe renal cell carcinomas and three primary chromophobe renal cell carcinomas with distant metastases. A cytogenetic analysis by fluorescent in situ hybridization on paraffin-embedded tissue was performed using centromeric probes for chromosomes 1, 2, 6, 10 and 17. We found more than one signal in four of six (66%) sarcomatoid chromophobe renal cell carcinomas, in both sarcomatoid and adjacent epithelial components. Both primary chromophobe renal cell carcinomas and matched metastases showed single signals for all chromosomes studied in two cases and no abnormalities in the remaining case. We concluded that: (1) both epithelial and sarcomatoid components of sarcomatoid chromophobe renal cell carcinoma show different genetic abnormalities from those characteristic of chromophobe renal cell carcinoma; (2) sarcomatoid chromophobe renal cell carcinomas frequently have multiple gains (polysomy) of chromosomes 1, 2, 6, 10 and 17; (3) distant metastases show the same genetic patterns, usually chromosomal losses (monosomy), found in the primary tumors. Keywords: sarcomatoid chromophobe renal carcinoma; metastases; FISH; cytogenetic Most chromophobe renal cell carcinomas are low stage, cured by surgery and have a relatively good prognosis. 1 Losses of chromosomes 1, 2, 6, 10 and 17 are frequent genetic abnormalities in both classic and eosinophilic chromophobe renal cell carcinomas. 2 Chromophobe renal cell carcinomas with distant metastases or sarcomatoid transformation are uncommon. [3][4][5][6] Most have been reported as single cases [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] and few cytogenetic data are available. 24 We sought to identify cytogenetic characteristics of sarcomatoid and metastatic chromophobe renal cell carcinomas by interphase fluorescence in situ hybridization (FISH) analysis. Materials and methods Tissue Samples, Histochemical and Immunohistochemical AnalysesWe collected six chromophobe renal cell carcinomas with sarcomatoid transformation and three primary chromophobe renal cell carcinomas with matched distant metastases. Two cases with sarcomatoid features were collected from the

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Section: Discussionmentioning

confidence: 61%

Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma

et al. 2007

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“…With 10% of all RCCs, pRCC represents the most frequent RCC subtype after ccRCC (80%) (Motzer et al, 1996;Kovacs et al, 1997). Although deletion on chromosome 3 with the VHL gene residing on 3p25 has been clearly linked to ccRCC, genetic heterogeneity in pRCC is diverse, often involving chromosomal trisomies/tetrasomies in chromosome 7 and 17, as well as losses of chromosome Y (reviewed by Moch and Mihatsch, 2002). Cdr2 is localized on 16p12.3 and genetically not linked to pRCC.…”

Section: Discussionmentioning

confidence: 99%

Onconeuronal cerebellar degeneration-related antigen, Cdr2, is strongly expressed in papillary renal cell carcinoma and leads to attenuated hypoxic response

Balamurugan

et al. 2009

Oncogene

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The onconeuronal cerebellar degeneration-related antigen Cdr2 is associated with paraneoplastic syndromes. Neoplastic expression of Cdr2 in ovary and breast tumors triggers an autoimmune response that suppresses tumor growth by developing tumor immunity, but culminates in cerebellar degeneration when Cdr2-specific immune cells recognize neuronal Cdr2. We identified Cdr2 as a novel interactor of the hypoxia-inducible factor (HIF) prolyl-4-hydroxylase PHD1 and provide evidence that Cdr2 might represent a novel important tumor antigen in renal cancer. Strong Cdr2 protein expression was observed in 54.2% of papillary renal cell carcinoma (pRCC) compared with 7.8% of clear-cell RCC and no staining was observed in chromophobe RCC or oncocytoma. High Cdr2 protein levels correlated with attenuated HIF target gene expression in these solid tumors, and Cdr2 overexpression in tumor cell lines reduced HIF-dependent transcriptional regulation. This effect was because of both attenuation of hypoxic protein accumulation and suppression of the transactivation activity of HIF-1a. pRCC is known for its tendency to avascularity, usually associated with a lower pathological stage and higher survival rates. We provide evidence that Cdr2 protein strongly accumulates in pRCC, attenuates the HIF response to tumor hypoxia and may become of diagnostic importance as novel renal tumor marker.

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“…To better understand the molecular mechanisms of RCC, several cytogenetic and molecular genetic approaches have been used to identify the genetic alterations underlying this disease (4). Conventional G-banding, loss of heterozygosity, and comparative genomic hybridization have all contributed to consistent and reliable correlation between chromosomal alterations and histological subtypes, leading to a proposed molecular subclassification model for RCC (5,6).…”

Section: Introductionmentioning

confidence: 99%

Robust Classification of Renal Cell Carcinoma Based on Gene Expression Data and Predicted Cytogenetic Profiles

et al. 2004

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Renal cell carcinoma (RCC) is a heterogeneous disease that includes several histologically distinct subtypes. The most common RCC subtypes are clear cell, papillary, and chromophobe, and recent gene expression profiling studies suggest that classification of RCC based on transcriptional signatures could be beneficial. Traditionally, however, patterns of chromosomal alterations have been used to assist in the molecular classification of RCC. The purpose of this study was to determine whether it was possible to develop a classification model for the three major RCC subtypes that utilizes gene expression profiles as the bases for both molecular genetic and cytogenetic classification. Gene expression profiles were first used to build an expression-based RCC classifier. The RCC gene expression profiles were then examined for the presence of regional gene expression biases. Regional expression biases are genetic intervals that contain a disproportionate number of genes that are coordinately upor down-regulated. The presence of a regional gene expression bias often indicates the presence of a chromosomal abnormality. In this study, we demonstrate an expression-based classifier can distinguish between the three most common RCC subtypes in 99% of cases (n ‫؍‬ 73). We also demonstrate that detection of regional expression biases accurately identifies cytogenetic features common to RCC. Additionally, the in silicoderived cytogenetic profiles could be used to classify 81% of cases. Taken together, these data demonstrate that it is possible to construct a robust classification model for RCC using both transcriptional and cytogenetic features derived from a gene expression profile.

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Genetic progression of renal cell carcinoma

Cited by 20 publications

References 59 publications

Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma

Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma

Onconeuronal cerebellar degeneration-related antigen, Cdr2, is strongly expressed in papillary renal cell carcinoma and leads to attenuated hypoxic response

Robust Classification of Renal Cell Carcinoma Based on Gene Expression Data and Predicted Cytogenetic Profiles

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