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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previously studied family with inherited renal cell carcinoma (RCC), RCC was shown to segregate with a constitutional balanced t(3;8)(p14.2;q24.1). In addition, we recently showed that in a RCC tumor from this family the constitutional translocation became unbalanced, suggesting a genetic mechanism that may be associated with the primary genetic events of tumorigenesis. We now report that the RCC tumor cells from this case showed additional cytogenetic alterations, possibly related to tumor progression, which include an additional tumor-specific translocation involving band 14 of chromosome 13. Because this band contains the retinoblastoma (RB) gene, we examined the tumor for aberrations in the RB gene using DNA sequence polymorphism analysis and pulsed-field gel electrophoresis (PFGE), but did not detect alterations in the RB gene.
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PMID:Cytogenetic and molecular studies of a familial renal cell carcinoma. 142 22

Tumor cells from direct harvests and short term cultures were karyotyped from 15 patients with transitional cell carcinoma of the bladder. There were two tumors with an apparently normal diploid karyotype, eight with counts up to 50 and with marker chromosomes, and five with counts of 60 or more and with markers. The median duration between recurrences was 3 months for the near-diploid, and 3 months for the near-polyploid tumors. One patient whose tumor was normal diploid had a recurrence at 5 months and the second patient whose tumor had normal diploid tumor had no recurrence over 15 months. Four tumors (27% of the series) had a rearrangement involving band 3p14: three had +der(5)t(3;5)(p14;p14) and one had +der(6)t(1;3;6)(q21;p14;p23). Duplication 3p14----3pter was observed in four tumors, and deletion 11p15----11pter in five. Three other abnormalities were observed in three cases each: deletion 5p14----5pter, duplication 1q23----1q32 and deletion 6q21----6qter. Trisomy 7 was observed as a sole clonal abnormality in one carcinoma in situ. Thirteen of 15 patients had recurrence of their tumor. Tumor progression (either in stage or grade) was evident in seven recurrent tumors. Among the seven with tumor progression, three had 11p deletion, two had 11p deletion plus 3p duplication, one had 3p duplication, and one had trisomy 7. Four of the five that had 11p deletion underwent cystectomy and three have died. Three of eight near-diploid tumors progressed and four of five near-tetraploid tumors progressed. It will be important to characterize any cytogenetic changes that are of prognostic value, since the categorization of bladder tumors by other methods has been problematic.
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PMID:Tumor behavior in transitional cell carcinoma of the bladder in relation to chromosomal markers and histopathology. 347 51

We compared the cytogenetic pattern of 20 different primary tumor cell cultures (PTCC) of renal cell carcinoma (RCC) to their cytokine secretion and oncogene expression. High secretion of IL-6 (gene locus on chromosome 7p21-p14) was correlated with the gain of an additional chromosome 7. Structural changes involving chromosome 5q22, the site of the GM-CSF gene, were matched with the high secretion of GM-CSF in PTCC. No such association was found for beta 2-microglobulin, TGF-beta 1, TNF-alpha, IL-8, and oncogenes, such as c-fos, c-myc, and pan-ras. Our approach may be useful in simultaneously analyzing several factors contributing to tumor progression and may contribute to understanding the multistep development of RCC.
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PMID:Comparison of cytogenetics, cytokine secretion, and oncogene expression in primary cultures of renal carcinoma cells. 926 Jun 6

Elevation of p16, the CDKN2/p16 tumor suppressor gene (TSG) product, occurs at senescence in normal human uroepithelial cells (HUC). Immortal HUCs and bladder cancer cell lines show either alteration of p16 or pRb, the product of the retinoblastoma (RB) TSG. In addition, many human cancers show p16 or pRb alteration along with other genetic alterations that we associated with immortalization, including +20q and -3p. These observations led us to hypothesize that p16 elevation plays a critical role in senescence cell cycle arrest and that overcoming this block is an important step in tumorigenesis in vivo, as well as immortalization in vitro. Using a novel approach, we tested these hypotheses in the present study by examining p16 and pRb status in primary culture (P0) and after passage in vitro of transitional cell carcinoma (TCC) biopsies that represented both superficial bladder tumors and invasive bladder cancers. We demonstrated that all superficial TCCs showed elevated p16 after limited passage in vitro and then senesced, like normal HUCs. In contrast, all muscle invasive TCCs contained either a p16 or a pRb alteration at P0 and all spontaneously bypassed senescence (P = 0.001). Comparative genomic hybridization (CGH) was used to identify regions of chromosome loss or gain in all TCC samples. The application of a statistical model to the CGH data showed a high probability of elevated alteration rates of +20q11-q12 (0.99) and +8p22-pter (0.94) in the immortal muscle invasive TCCs, and of -9q (0.99) in the superficial TCCs. Three myoinvasive TCCs lost 3p13-p14. In this study, four of six myoinvasive TCCs also showed TP53 mutation that associated well with genome instability (P = 0.001), as previously hypothesized. Notably, TP53 mutation, which has been used as a marker of tumor progression in many human cancers, was less significant in associating with progression in this study (P = 0.04) than was p16 or pRb alteration (P = 0.001). Thus, these data support a new model in which overcoming senescence plays a critical role in human cancer pathogenesis and requires at least two genetic changes that occur in several combinations that can include either p16 or pRb loss and at least one additional alteration, such as +20q11-q12, -3p13-p14, or -8p21-pter.
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PMID:Overcoming cellular senescence in human cancer pathogenesis. 943 77

DNA copy number changes were characterized by comparative genomic hybridization (CGH) in 18 breast cancer cell lines. In 5 of these, the results were comparable with those from the primary tumors of which the cell lines were established. All of the cell lines showed extensive DNA copy number changes, with a mean of 16.3 +/- 1.1 aberrations per sample (range 7-26). All of the cell lines had a gain at 8q22-qter. Other common gains of DNA sequences occurred at 1q31-32 (89%), 20q12-q13.2 (83%), 8q13 (72%), 3q26.1-qter (67%), 17q21-qter (67%) 5p14 (61%), 6p22 (56%), and 22pter-qter (50%). High-level amplifications were observed in all cell lines; the most frequent minimal common regions were 8q24.1 (89%), 20q12 (61%), 1q41 (39%), and 20p11.2 (28%). Losses were observed less frequently than gains and the minimal common regions of the most frequent losses were Xq11-q12 (56%), Xp11.2-pter (50%), 13q21 (50%), 8p12-pter (44%), 4p13-p14 (39%), 6q15-q22 (39%), and 18q11.2-qter (33%). Although the cell lines showed more DNA copy number changes than the primary tumors, all aberrations, except one found in a primary tumor, were always present in the corresponding cell line. High-level amplifications found both in primary tumors and cell lines were at 1q, 8q, 17q, and 20q. The DNA copy number changes detected in these cell lines can be valuable in investigation of tumor progression in vitro and for a more detailed mapping and isolation of genes implicated in breast cancer.
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PMID:Comparative genomic hybridization reveals complex genetic changes in primary breast cancer tumors and their cell lines. 1086 49

Recent studies have identified several chromosome regions that are altered in primary prostate cancer and prostatic carcinoma cell lines. These targeted regions may harbor genes involved in tumor suppression. We used multiplex fluorescence in situ hybridization (M-FISH) to screen for genetic rearrangements in four prostate cancer cell lines, LNCaP, LNCaP.FCG, DU145, and PC3, and compared our results with those recently obtained using spectral karyotyping (SKY). A number of differences was noted between abnormalities characterized by SKY and M-FISH, suggesting variation in karyotype evolution and characterization by these two methodologies. M-FISH analysis showed that hormone-resistant cell lines (DU145 and PC3) contained many genetic alterations (> or =15 per cell), suggesting high levels of genetic instability in hormone-refractory prostate cancer. Most chromosome regions previously implicated in prostate cancer were altered in one or more of these cell lines. Several specific chromosome aberrations were also detected, including a del(4)(p14) and a del(6)(q21) in the hormone-insensitive cell lines, a t(1;15)(p?;q?) in LNCaP, LNCaP, and PC3, and a i(5p) in LNCaP.FCG, DU145, and PC3. These clonal chromosome abnormalities may pinpoint gene loci associated with prostate tumourigenesis, cancer progression, and hormone sensitivity.
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PMID:The use of multicolor fluorescence technologies in the characterization of prostate carcinoma cell lines: a comparison of multiplex fluorescence in situ hybridization and spectral karyotyping data. 1117 1

T-cell prolymphocytic leukemia (T-PLL) is a rare malignant proliferation of lymphoid cells with a postthymic phenotype. Previous cytogenetic and molecular studies reported complex karyotypes with recurrent chromosomal abnormalities, including translocations involving either TCL1 at 14q32.1 or MTCP1 at Xq28, inactivation of the ATM gene by deletion and/or mutation, and isochromosomes 8. For extensive study of chromosomal imbalances in T-PLL, we analyzed 22 tumoral DNAs using comparative genomic hybridization (CGH). Abnormal CGH profiles were detected in all cases, demonstrating highly recurrent gains and losses and largely extending the abnormalities previously established. Only a few nonrecurrent abnormalities were observed, in contrast to the genetic instability anticipated from ATM inactivation. Nine recurrent regions of loss were identified at 8p (frequency 86%), 11q (68%), 22q11 (45%), 13q (41%), 6q (36%), 9p (27%), 12p (23%), 11p11-p14 (23%), and 17p (23%), as well as four regions of gain at 8q (82%), 14q32 (50%), 22q21-qter (41%), and 6p (23%). Several recurrent chromosomal abnormalities were simultaneously present in each case (mean, 5.7; up to 10), none being mutually exclusive of another. Fluorescence in situ hybridization analysis confirmed and extended 22q11 and 13q losses, giving final frequencies of 55% and 45%, respectively. Analysis of one case over a 7-year period confirmed the overall genetic stability of T-PLL and showed that tumor progression was associated with the onset of a few chromosomal abnormalities. This study establishes a complex pattern of highly recurrent chromosomal abnormalities in T-PLL, including some, such as chromosome 13 deletion, commonly found in other lymphoid malignancies.
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PMID:A complex pattern of recurrent chromosomal losses and gains in T-cell prolymphocytic leukemia. 1139 95

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma, a cancer of which the incidence has been increasing at an alarming rate in Western countries. p16(INK4a) lesions occur frequently in esophageal adenocarcinomas but their role in neoplastic progression is not well understood. We detected 9p21 loss of heterozygosity, p16 CpG island methylation, and p16 mutations in biopsies from 57%, 61%, and 15%, respectively, of 107 patients with BE. In contrast, no mutations were found in p14(ARF) or p15, and methylation was found in only 4% and 13%, respectively. >85% of Barrett's segments had clones with one (p16+/-) or two (p16-/-) p16 lesions. Both p16+/- and p16-/- clones underwent extensive expansion involving up to 17 cm of esophageal mucosa. The prevalence of established biomarkers in BE, such as 17p (p53) loss of heterozygosity, aneuploidy, and/or increased 4N (tetraploid) populations, increased from 0% to 20% to 44% in patients whose biopsies were p16+/+, p16+/-, and p16-/-, respectively (P < 0.001). Barrett's segment lengths also increased with change in p16 status with a median of 1.5, 6.0, and 8.0 cm for patients with p16+/+, p16+/-, and p16-/- biopsies, respectively (P < 0.001). We conclude that most Barrett's metaplasia contains genetic and/or epigenetic p16 lesions and has the ability to undergo clonal expansion, creating a field in which other abnormalities can arise that can lead to esophageal adenocarcinoma.
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PMID:p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett's metaplastic epithelium. 1171 61

The INK4a / ARF locus on chromosome 9p21, which encodes two distinct genes, p14(ARF) and p16(INK4a), is frequently altered in human neoplasms. To investigate the potential roles of p14(ARF) and p16(INK4a) genes in human renal cell carcinomas (RCCs), we analyzed 6 human RCC cell lines and 91 primary RCCs for homozygous deletion, promoter hypermethylation and expression of the p14(ARF) and p16(INK4a) gene products using differential PCR, methylation-specific PCR, and immunohistochemistry, respectively. Five cell lines showed homozygous co-deletion of both genes and one demonstrated promoter hypermethylation of the p16(INK4a) gene only. Eight of 91 RCCs showed aberrations of p14(ARF) or p16(INK4a) status and six of these featured gross extension into the renal vein. The results suggest that p14(ARF) and p16(INK4a) aberrations may play roles in the relatively late stage of renal tumorigenesis associated with tumor progression.
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PMID:Aberrations of the p14(ARF) and p16(INK4a) genes in renal cell carcinomas. 1174 94

Sixty-one glioblastomas have been studied, subdivided into the categories of classic glioblastomas (GBM) and glioblastomas with astrocytic (GBA) and oligodendroglial (GBO) differentiated areas. On surgical samples, TP53, Mdm2, CDKN2A/p16-p14 alterations were studied by molecular biology techniques and by immunohistochemistry. It has been found that Mdm2 amplification was more frequent in GBM than in GBA and GBO, that p14ARF was inactivated in a high percentage of cases in the three tumor categories. Both these and other alterations did not reach a statistical significance, with the exception of CDKN2A/p16 homozygous deletion which showed the highest frequency in GBO. The latter finding could be in line with the observation that CDKN2A/p16 inactivation is a step in the molecular pathway to tumor progression in oligodendrogliomas. TP53 mutations and Mdm2 amplifications were mutually exclusive, whereas TP53 mutations and CDKN2A/p14 inactivation coexisted in 5 cases. The alterations of the p53/Mdm2/p14ARF pathway occurred in 73% of cases and in 80% of cases if CDKN2A homozygous deletions were associated. All glioblastomas with gemistocytic areas showed p14ARF inactivation. Immunohistochemistry showed higher percentages of positivity in comparison with molecular genetics, but with similar variations.
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PMID:Deregulation of the p14ARF/Mdm2/p53 pathway and G1/S transition in two glioblastoma sets. 1262 47


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