Biomedical subjects

P Schraml

Publications and source records attributed to P Schraml.

At least 19 recordsLinked to original sources

PubMed2000

Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques.

New genomic large-scale screening techniques have made the task of establishing an accurate molecular fingerprint of cancer cells feasible. Here, we have used a two-phase strategy for identification of molecular alterations in gliomas. First, cDNA microarrays (Clontech Laboratories, Inc., Research Genetics) were used to pinpoint differentially expressed genes between normal brain and diffuse astrocytomas (grades II-IV), and between a primary tumor and a later tumor reoccurrence in the same patient. More than 200 gene expression alterations were detected from glioblastomas, whereas relatively few changes were seen in grade II and grade III tumors. The most distinct progression-related expression change was the up-regulation of the insulin-like growth factor binding protein 2 (IGFBP2) gene. Second, a high-density tissue microarray of 418 brain tumors was constructed and used for clinical validation of gene expression changes. Strong expression of IGFBP2 was associated with progression and poor patient survival in diffuse astrocytomas (P < 0.0001). Third, comparisons of the data between (a) multiple spots retrieved from one predefined tumor region (IGFBP2 and vimentin immunohistochemistry, 20 tumors) or between (b) standard slides and arrayed tissues (p53 immunohistochemistry, 42 tumors) revealed very little variation. In conclusion, the combined use of DNA microarrays and tissue microarrays offers a powerful strategy for rapid identification and thorough characterization of differentially expressed genes in gliomas.

Astrocytoma↗

PubMed2000

Construction of evolutionary tree models for renal cell carcinoma from comparative genomic hybridization data.

Renal cell carcinoma is characterized by an accumulation of complex chromosomal alterations during tumor progression. Chromosome 3p deletions are known to occur early in the carcinogenesis, but the nature of subsequent events, their interrelationships, and their sequence is poorly understood, as one usually only obtains a single "view" of the dynamic process of tumor development in a particular cancer patient. To address this limitation, we used comparative genomic hybridization analysis in combination with a distance-based and a branching-tree method to search for tree models of the oncogenesis process of 116 conventional (clear cell) renal carcinomas. This provides a means to analyze and model cancer development processes based on a more dynamic model, including the presence of multiple pathways, as compared with the fixed linear model first proposed by Vogelstein et al. (N. Engl. J. Med., 319: 525-532, 1988) for colorectal cancer. The most common DNA losses involved 3p (61%), 4q (50%), 6q (40%), 9p (35%), 13q (37%), and Xq (21%). The most common gains were seen at chromosome 17p and 17q (20%). The tree model derived from the distance-based method is consistent with the established theory that -3p is an important early event in conventional (clear cell) renal cancer and supports the prediction made from the branching tree that -4q is another important early event. Both tree models suggest that there may be two groups of clear cell renal cancers: one characterized by -6q, +17q, and + 17p, and another by -9p, -13q, and -18q. Putative prognostic parameters were -9p and -13q. The distance-based tree clarifies that -8p (present in 12% of tumors) is a late event, largely independent of other events. In summary, tree modeling of comparative genomic hybridization data provided new information on the interrelationships of genetic changes in renal cancer and their possible order, as well as a clustering of these events. Using tree analysis, one can derive a more in-depth understanding of the renal cancer development process than is possible by simply focusing on the frequencies of genetic events in a given cancer type.

Carcinoma, Renal Cell↗

PubMed2000

Identification of genes differentially expressed in melanoma sublines derived from a single surgical specimen characterised by different sensitivity to cytotoxic T-lymphocyte activity.

In this study we used differential display technology in an attempt to obtain an insight into the mechanisms underlying escape of tumour cells to the specific cytotoxic T cell response. A primary tumour cell line and autologous tumour infiltrating lymphocytes were raised from a metastatic melanoma sample (ME15). Upon co-culture of tumour infiltrating lymphocytes with irradiated tumour cells, CTL specific for neoplastic cells were generated and cloned. Using a CTL clone, a cytotoxicity resistant tumour subline (ME15R) was immunoselected. We applied a PCR-based differential display technique to amplify DNA sequences differentially expressed in ME15 sublines sensitive (S) or resistant (R) to specific CTL killing. 10 different sequences whose expression was exclusively detectable in ME15S cells were identified. Five of them matched with known expressed sequence tags encoding products of unidentified function. 2 showed high homology with a mitochondrial mRNA and with the gene encoding the S24 ribosomal protein. Most interestingly, genes coding for glutamine synthetase, TGF-beta-3 and PAX3, a well-characterised transcription factor, were only expressed in ME15S cells. The latter gene was found to be transcribed in all healthy tissues tested, but only in a subgroup of established melanoma cell lines. Taken together, our data underline the relevant potential of differential display technology in the molecular analysis of paired tumour lines endowed with different phenotypic characteristics. Cloning of entire open reading frames and transfection studies are warranted to clarify the role of individual differentially displayed genes in the escape of tumour cells from cellular immune response.

Base Sequence↗

PubMed2000

Allelic loss at the D9S171 locus on chromosome 9p13 is associated with progression of papillary renal cell carcinoma.

Papillary renal cell carcinomas (RCCs) have characteristic clinical and morphological features that separate them from the more common clear cell RCCs. The details of the molecular changes in papillary RCC progression are not well understood. In this study, four highly polymorphic microsatellite markers [D9S970 (9p12-9p13), D9S171 (9p13), D9S1748 (9p21) and D9S156 (9p21)] were used to determine the frequency and prognostic significance of 9p deletions in 37 papillary RCCs. Allelic deletions were detected in eight cases (22%). The highest rate of loss of heterozygosity (LOH) was observed in 6 of 29 informative patients (21%) at the D9S171 locus on 9p13. Only two patients displayed allelic loss at D9S1748, which resides in close proximity to p16(INK4). Two of 24 informative papillary RCCs (8%) showed LOH for D9S970. LOH at D9S171 (9p13) was associated with short patient survival (p=0.008), independently of tumour grade and stage. These data suggest a tumour suppressor gene centromeric to 9p21 that may contribute to papillary RCC progression.

Carcinoma, Papillary↗

PubMed2000

High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the 19q13 chromosomal region is frequently amplified in bladder cancer. The cyclin E gene (CCNE), coding for a regulatory subunit of cyclin-dependent kinase 2, has been mapped to 19q13. To investigate the role of cyclin E alterations in bladder cancer, a tissue microarray of 2,317 specimens from 1,842 bladder cancer patients was constructed and analyzed for CCNE amplification by fluorescence in situ hybridization and for cyclin-E protein overexpression by immunohistochemistry. Fluorescence in situ hybridization analysis showed amplification in only 30 of the 1,561 evaluable tumors (1.9%). Amplification was significantly associated with stage and grade (P: < 0.0005 each). Immunohistochemically detectable cyclin E expression was strong in 233 (12.4%), weak in 354 (18.9%), and negative in 1, 286 of the 1,873 interpretable tumors. The majority (62.1%) of CCNE-amplified tumors were strongly immunohistochemistry-positive (P: < 0.0001). The frequency of protein expression increased from stage pTa (22.2%) to pT1 (45.5%; P: < 0.0001) but then decreased for stage pT2-4 (29.4%; P: < 0.0001 for pT1 versus pT2-4). Low cyclin E expression was associated with poor overall survival in all patients (P: < 0.0001), but had no prognostic impact independent of stage. It is concluded that cyclin E overexpression is characteristic to a subset of bladder carcinomas, especially at the stage of early invasion. This analysis of the prognostic impact of CCNE gene amplification and protein expression in >1,500 arrayed bladder cancers was accomplished in a period of 2 weeks, illustrating how the tissue microarray technology remarkably facilitates the evaluation of the clinical relevance of molecular alterations in cancer.

Adult↗

PubMed1999

Chromosomal imbalances are associated with a high risk of progression in early invasive (pT1) urinary bladder cancer.

Many cytogenetic alterations are known to occur in urinary bladder cancer, but the significance of most of them is poorly understood. To define these chromosomal regions where clinically relevant genes may be located, a series of 54 pT1 urinary bladder carcinomas with clinical follow-up information (median, 52 months; range, 5-167 months) were examined by comparative genomic hybridization. The most frequent alterations included DNA sequence copy number gains at 1q22-24 (33%), 20q11.2-ter (33%), 8q22 and 17q21 (28% each), and 6p22 (15%) as well as deletions at Y (37%), 9p (31%), 9q22-33 and 11p14-ter (28% each), 11q23 (26%), 8p (24%), 13q31 (19%), 2q35-ter (17%), and 2q22-33 (11%). Whereas the histological grade was unrelated to prognosis (P = 0.9752), the risk of tumor progression was significantly associated with the number of deletions per tumor (P = 0.0014). Individual cytogenetic alterations that were linked to subsequent tumor progression included gains of 3p22-24 (P = 0.0112) and 5p (P = 0.0003) as well as losses of 4p11-15 (P = 0.0052), 5q15-23 (P = 0.0410), 6q22-23 (P = 0.0090), 10q24-26 (P = 0.0232), and 18q12-23 (P = 0.0005). Genes with a role for bladder cancer progression may be located at these regions.

Carcinoma↗

PubMed1999

Hormone therapy failure in human prostate cancer: analysis by complementary DNA and tissue microarrays.

BACKGROUND: The molecular mechanisms underlying the progression of prostate cancer during hormonal therapy have remained poorly understood. In this study, we developed a new strategy for the identification of differentially expressed genes in hormone-refractory human prostate cancer by use of a combination of complementary DNA (cDNA) and tissue microarray technologies. METHODS: Differences in gene expression between hormone-refractory CWR22R prostate cancer xenografts (human prostate cancer transplanted into nude mice) and a xenograft of the parental, hormone-sensitive CWR22 strain were analyzed by use of cDNA microarray technology. To validate the data from cDNA microarrays on clinical prostate cancer specimens, a tissue microarray of specimens from 26 prostates with benign prostatic hyperplasia, 208 primary prostate cancers, and 30 hormone-refractory local recurrences was constructed and used for immunohistochemical detection of protein expression. RESULTS: Among 5184 genes surveyed with cDNA microarray technology, expression of 37 (0.7%) was increased more than twofold in the hormone-refractory CWR22R xenografts compared with the CWR22 xenograft; expression of 135 (2.6%) genes was reduced by more than 50%. The genes encoding insulin-like growth factor-binding protein 2 (IGFBP2) and 27-kd heat-shock protein (HSP27) were among the most consistently overexpressed genes in the CWR22R tumors. Immunohistochemical analysis of tissue microarrays demonstrated high expression of IGFBP2 protein in 100% of the hormone-refractory clinical tumors, in 36% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). Overexpression of HSP27 protein was demonstrated in 31% of the hormone-refractory tumors, in 5% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). CONCLUSIONS: The combination of cDNA and tissue microarray technologies enables rapid identification of genes associated with progression of prostate cancer to the hormone-refractory state and may facilitate analysis of the role of the encoded gene products in the pathogenesis of human prostate cancer.

Animals↗

PubMed1999

Chromosomal imbalances in noninvasive papillary bladder neoplasms (pTa).

Almost 70% of urinary bladder neoplasms present as low-grade papillary noninvasive tumors (stage pTa). To determine which genomic alterations can occur in pTa tumors of different grades and to evaluate the prognostic significance of chromosomal imbalances, we analyzed 113 pTa tumors (40 grade 1, 55 grade 2, 18 grade 3) by comparative genomic hybridization. pTaG1 (1.9 +/- 2.0) and pTaG2 (3.1 +/- 2.9) tumors had only few genomic alterations with 9q- (44%), 9p- (36%), and -Y (21%) being most prevalent. Neither the total number of aberrations nor any individual alteration was linked to the risk of recurrence in 95 pTaG1/G2 tumors with clinical follow-up information. pTaG3 tumors were characterized by a high number of alterations (7.7 +/- 4.5; P < 0.0001 for G3 versus G2). Several chromosomal imbalances that have previously been reported to be typical for invasive bladder neoplasms were significantly more frequent in pTaG3 than in pTaG2 tumors, including 2q-, 5p+, 5q-, 6q-, 8p-, 10q-, 18q-, and 20q+. A malfunction of genes at these loci may contribute to the development of high-grade urothelial neoplasias. However, there is no evidence for a direct role of these alterations for development of invasive tumor growth.

Carcinoma in Situ↗

PubMed1999

Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays.

Prostate cancer development and progression is driven by the accumulation of genetic changes, the nature of which remains incompletely understood To facilitate high-throughput analysis of molecular events taking place in primary, recurrent, and metastat prostate cancer, we constructed a tissue microarray containing small 0.6-mm cylindrical samples acquired from 371 formalin-fixed blocks, including benign prostatic hyperplasia (n = 32) and primary tumors (n = 223), as well as both locally recurrent tumors (n = 54) and metastases (n = 62) from patients with hormone-refractory disease. Fluorescence in situ hybridization (FISH) was applied to the analysis of consecutive tissue microarray sections with probes for five different genes. High-level (> or =3X) amplifications were very rare (<2%) in primary prostate cancers However, in metastases from patients with hormone-refractory disease, amplification of the androgen receptor gene was seen in 22%, MYC in 11%, and Cyclin-D1 in 5% of the cases. In specimens from locally recurrent tumors, the corresponding percentages were 23, 4, and 8%. ERBB2 and NMYC amplifications were never detected at any stage of prostate cancer progression. In conclusion, FISH to tissue microarray sections enables high-throughput analysis of genetic alterations contributing to cancer development and progression. Our results implicate a role for amplification of androgen receptor in hormonal therapy failure and that of MYC in the metastatic progression of human prostate cancer.

Cyclin D1↗

PubMed1999

Evaluation of the clonal relationship between primary and metastatic renal cell carcinoma by comparative genomic hybridization.

The outcome of patients with renal cell carcinoma is limited by the development of metastasis after nephrectomy. To evaluate the genetic basis underlying metastatic progression of human renal cell carcinoma in vivo, we performed a comparative genomic hybridization analysis in 32 clear-cell renal-cell carcinoma metastases. The most common losses involved chromosomes 3p (25%), 4q (28%), 6q (28%), 8p (31%), and 9p (47%). The most common gains were detected at 17q (31%) and Xq (28%). There was one high-level gene amplification at chromosome 11q22-23. The mean number of aberrations in lymph node (4.8 +/- 2.8) and lung metastases (6.2 +/- 4.0) was lower than in other hematogenous metastases (11.5 +/- 8.7, P < 0.05), suggesting that hematogenous dissemination is linked to an acquisition of complex genomic alterations. As genetic differences between primary tumors and metastases give information on genetic changes that have contributed to the metastatic process, relative DNA sequence copy number changes in 19 matched tumor pairs were compared. Genomic changes, which frequently occurred in metastases but not in the corresponding primary tumor were losses of 8p and 9p and gains of 17q and Xq. An abnormal function of genes in these regions may contribute to the metastatic process. According to a statistical analysis of shared genetic changes in matched tumor pairs, a high probability of a common clonal progenitor was found in 11 of 19 patients (58%). Six metastases (32%) were genetically almost completely different from the primary, suggesting that detection of genomic alterations in primary tumors gives only a restricted view of the biological properties of metastatic renal cell carcinoma.

Carcinoma, Renal Cell↗

PubMed1999

High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma.

Many genes and signaling pathways are involved in renal cell carcinoma (RCC) development. However, genetic tumor markers have not gained use in RCC diagnostics and prognosis prediction. Identification and evaluation of new molecular parameters are of utmost importance in cancer research and cancer treatment. Here we present a novel approach to rapidly identify clinically relevant molecular changes in cancer. To identify genes with relevance to RCC, a cDNA array analysis was first performed on 5184 cDNA clones on a filter to screen for genes with differential expression between the renal cancer cell line CRL-1933 and normal kidney tissue. There were 89 differentially expressed genes in the cancer cell line, one of them coding for vimentin, a cytoplasmic intermediate filament. In a second step, a renal cancer tissue microarray containing 532 RCC specimen was used to determine vimentin expression by immunohistochemistry. Vimentin expression was seen frequently in clear cell (51%) and papillary RCC (61%), but rarely in chromophobe RCC (4%) and oncocytomas (12%). Furthermore, vimentin expression was significantly associated with poor patient prognosis (P < 0.007) independent of grade and stage. These results obtained from minute arrayed tumor samples match well with previous findings on vimentin expression in renal tumors. It is concluded that the combination of tumor arrays and cDNA arrays is a powerful approach to rapidly identify and further evaluate genes that play a role in tumor biology.

Carcinoma, Renal Cell↗

PubMed1999

Tissue microarrays for gene amplification surveys in many different tumor types.

Gene amplifications are common in many different tumor types and may confer diagnostic, prognostic, or therapeutic information for patient management. Tedious experiments are often required to determine which tumor types have amplifications of a specific oncogene. To facilitate rapid screening for molecular alterations in many different malignancies, a tissue microarray consisting of samples from 17 different tumor types was generated. Altogether, 397 individual tumors were arrayed in a single paraffin block. To determine whether results from the literature can be reproduced on minute tissue samples (diameter, 0.6 mm), amplification of three extensively studied oncogenes (CCND1, CMYC, and ERBB2) was analyzed in three fluorescence in situ hybridization experiments from consecutive sections cut from the tissue microarray. Amplification of CCND1 was found in breast, lung, head and neck, and bladder cancer, as well as in melanoma. ERBB2 was amplified in bladder, breast, colon, stomach, testis, and lung cancer. CMYC was amplified in breast, colon, kidney, lung, ovary, bladder, head and neck, and endometrial cancer. These results confirm and even extend existing data in the literature on such amplifications. In summary, we applied three fluorescence in situ hybridization experiments to analyze amplifications of three oncogenes in three x 397 tumors within a week. This demonstrates the power of using minute arrayed tissue specimens for tumor screening.

Cyclin D1↗

PubMed1999

[Analysis of kidney tumors in trichloroethylene exposed workers by comparative genomic hybridization and DNA sequence analysis].

Environmental and occupational mutagens such as chemical agents are suspected to be involved in cancer development. However, a direct link between carcinogen exposure and genetic alterations has been established only in a few examples. Carcinogen involvement in renal cell carcinoma (RCC) was recently supported by reports of an increased frequency of RCC among workers exposed to Trichloroethylene (TRI) in Germany. The aim of this study was to evaluate the phenotype and the genotype of renal tumors in occupationally TRI-exposed patients. Sporadic RCCs from TRI nonexposed patients served as control. Normal and renal tumor tissues from 12 patients with occupational histories of solvents and TRI exposure were histologically analyzed. Comparative Genomic Hybridization (CGH) was used to screen for genomic alterations along all chromosomal arms. Tumor DNA was analyzed for mutations of the von Hippel-Lindau gene (VHL) on 3p25.5 by PCR and sequencing analyses. The histological analysis revealed 9 clear cell (75%), 2 papillary RCC (18%) and 1 oncocytoma (8%). In clear cell RCC, DNA losses were frequently observed on 3p (66%), 6q (56%), 9p and 4q (44% each) and 2q (33%). DNA gains were detected on 9q, 17 (33% each) and 5q (22%). DNA gains were identified on chromosome 7 and 17 in papillary RCC. Four VHL gene mutations were found in three clear cell RCC (33%) with 3p loss. Comparisons of these results with data obtained from sporadic RCC revealed no unique phenotype, genotype or mutation pattern in the VHL gene of renal tumors after TRI exposure. Therefore, further studies on the relevance of dose and exposure time for the nephrocarcinogenic effect of TRI are indicated.

Base Sequence↗

PubMed1999

[Identification of prognostic parameters for renal cell carcinoma by cDNA arrays and cell chips].

We report here an example of how the combined application of cDNA and tumor array can lead to the identification of a novel prognostic marker within a very short time. A cDNA array analysis was performed on 5184 cDNA clones on a filter to screen for genes with differential expression between the renal cancer cell line CRL-1933 and normal kidney tissue to identify genes with relevance in RCC. There were 89 differentially expressed genes in the cancer cell line, one of them coding for vimentin, a cytoplasmic intermediate filament. To determine the in vivo prevalence and prognostic significance of vimentin expression, a renal cancer tissue micro array containing 532 RCC specimen was constructed and vimentin expression was determined by immunohistochemistry. Vimentin expression was frequently seen in clear-cell (51%) and papillary RCC (61%), but rarely in chromophobe RCC (4%) and oncocytomas (12%). These results obtained from minute arrayed tumor samples match with previous findings on vimentin expression in renal tumors. Furthermore, vimentin expression was significantly associated with poor patient prognosis (p < 0.007) independently of grade and stage. These results suggest that tissue microarray analysis provides a rapid and powerful method to determine the prevalence and prognostic significance of novel candidate genes discovered to be involved in cancer development with large-scale cDNA expression arrays. The tissue array can be adapted as a routine tool in research laboratories for analyses of large tumor series at the DNA, RNA or protein level. With such a tool, cancer researchers can study vast numbers of tumor samples in a short time and can generate a wealth of data on the application of tumor markers.

Biomarkers, Tumor↗

PubMed1998

Intratumoral heterogeneity of von Hippel-Lindau gene deletions in renal cell carcinoma detected by fluorescence in situ hybridization.

Although chromosome 3p deletions are considered an initial event in clear cell renal cell carcinoma (RCC), the reported prevalence of 3p deletions is highly variable. Because molecular analyses may be influenced by intratumoral heterogeneity, this study was performed to evaluate the genetic heterogeneity of the von Hippel-Lindau (VHL) gene (on 3p25.5) in RCC. Fifty-three clear cell and papillary RCCs were examined by dual-labeling fluorescence in situ hybridization with probes for the VHL gene and chromosome 3 centromere. The results were compared with histopathological phenotype, proliferative activity (Ki-67 labeling index) and 8p/17p deletions (both suggested to be linked to RCC progression). A clear-cut VHL deletion (in more than 40% of cells) was detectable in 69% of clear cell RCCs but was not detectable in nine papillary RCCs. A considerable genetic heterogeneity of VHL deletions was seen in clear cell RCCs including VHL-deleted subpopulations with different chromosome 3 counts within individual tumors as well as populations with and without VHL deletions. 8p22 and 17p13 deletions (each of which were detected in 18% of clear cell RCCs) were both linked to VHL deletions. However, 8p and 17p deletions were not associated with tumor grade, stage, or Ki-67 labeling index. The data indicate that some clear cell RCCs may develop independently of VHL alterations.

Carcinoma, Renal Cell↗

PubMed1998

Characterization of MAST9/Hevin, a SPARC-like protein, that is down-regulated in non-small cell lung cancer.

In the search for genes down-regulated in non-small cell lung cancer (NSCLC), we have identified a cDNA fragment, termed MAST9. Cloning, sequencing, and characterization of the full-length MAST9 cDNA revealed that the entire 2808 nucleotide sequence had an open reading frame of 1992 nucleotides encoding a Mr 75,000 protein. Sequence analysis disclosed a striking homology to SPARC, known to be involved in tumorigenesis. The recently identified "Hevin" cDNA isolated from high endothelial venules is identical to MAST9. Using Northern and Western blot analysis, we showed that MAST9 was down-regulated in the tumor samples of nine non-small cell lung carcinoma patients. Furthermore, we demonstrated that both the bacterially expressed and the endogenous MAST9 proteins form homodimers. The lack of expression in non-small cell lung carcinomas and its homology to SPARC suggest a putative role of MAST9 in lung tumor formation.

Amino Acid Sequence↗

PubMed1998

Chromosomal imbalances in papillary renal cell carcinoma: genetic differences between histological subtypes.

Papillary renal-cell carcinoma (RCC) is a renal carcinoma variant with distinct gross, microscopic, and cytogenetic features. Recently, a type 1 (pale cytoplasm, small-cell) and a type 2 (eosinophilic cytoplasm, large-cell) subtype of papillary RCC have been described. Chromosomal alterations associated with these tumor types were examined in 25 papillary RCCs by comparative genomic hybridization. Relative copy number gains were frequently detected at chromosomes 7p (56%), 7q (44%), 12q (28%), 16q (32%), 17p (56%), 17q (76%), and 20q (32%). Chromosomal regions that were most often lost included 1p (24%), 4q (36%), 6q (40%), 9p (36%), 13q (36%), Xp (28%), Xq (36%), and Y (73%). There were clinical and genetic differences between the subtypes of papillary RCC. Type 2 tumors were of higher nuclear grade (P = 0.0012) and higher stage (P = 0.01) and had a worse prognosis (P = 0.03) than type 1 tumors. The number of DNA gains per tumor, especially gains of 7p and 17p, was significantly higher in type 1 than in type 2 tumors (P < 0.01). These data suggest the existence of two distinct morphological and genetic subgroups of papillary RCC. Losses of chromosome Xp were associated with short patient survival (P < 0.01). Despite the small number of cases, this finding suggests that a gene on chromosome Xp may contribute to papillary RCC progression.

Carcinoma, Papillary↗

PubMed1998

Patterns of chromosomal imbalances in advanced urinary bladder cancer detected by comparative genomic hybridization.

To identify genetic changes linked to bladder cancer progression we analyzed 90 invasive transitional cell carcinomas (37 pT1 and 53 pT2-4) by comparative genomic hybridization. The most frequent alterations included 1q+ (37%), 5p+ (24%), 6q- (19%), 8p-(29%), 8q+ (37%), 9p- (31%), 9q- (23%), 11p-(24%), 11q- (22%), 17q+ (29%), and 20q+ (28%). Interestingly, there were three groups of alterations that frequently occurred together (9p- and 11q13+/ 20q+ and 11q13+ or 17q+/1q+ and 3p+ or 11q-). These loci might carry genes that interact with each other in specific molecular pathways. There were remarkable genetic similarities between minimally and deeply invasive tumors of different histological grades, including a similar number of aberrations per tumor and an equal frequency of most individual alterations. However, deletions of 5q, 6q, and 15q and gains of 5p, 7p, and Xq were significantly more frequent in pT2-4 than in pT1 carcinomas. These loci may harbor genes that are important for bladder cancer progression.

Chromosome Aberrations↗