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

Tumorigenesis is a multistep process involving mutations of dominantly acting proto-oncogenes and mutations and loss-of-function mutations of tumor suppressor genes. Some of these mutations may be inherited, but most of them are acquired. Models for the sequential steps of the genetic changes involved in tumor development have been proposed for certain cancers, such as colon cancer. In the case of ovarian cancer, relatively little is known about the genetic events associated with the initiation or subsequent progression and metastases of the tumor. Cytogenetic analysis has revealed a high incidence of both structural and numerical chromosome changes, and the extent of these changes seems to increase with tumor progression. Oncogene activations of the proto-oncogenes K-ras, c-myc and c-erbB-2 have been found more frequently in aggressive ovarian tumors and may be associated with poor survival. Tumor-specific allele loss involving putative tumor suppressor genes has been observed for loci at chromosomes 11p, 17p, and 17q,--loci commonly deleted in other cancers too. A relatively high incidence of allelic loss on chromosome 6q appears to be specific to ovarian carcinoma. Familial breast/ovarian cancer has been suggested to map to chromosome 8q. Recently we have found a germ-line mutation in the tumor suppressor gene p53 in a family with breast- and ovarian cancers, indicating that this is the predisposing gene in this family. Genetic changes important for the etiology of ovarian cancers seem to involve both somatic mutations of oncogenes and somatic or germ-line inactivation of tumor suppressor genes.
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PMID:Oncogenesis in ovarian cancer. 150 89

Loss of heterozygosity (LOH) of distal chromosome 4 was studied to localize a putative tumor suppressor gene in mouse lung neoplasia. Previous studies have implicated this region and its homologue on human chromosome 1p36-34 as sites of potential tumor suppressor genes. One hundred adenocarcinomas and 38 adenomas of the mouse lung were examined for LOH using nine simple sequence length polymorphism markers in a polymerase chain reaction-based approach. Forty-four adenocarcinomas displayed allele loss, all of which included losses at marker D4MIT54, which defined a critical region of 3 centiMorgans as the likely location of a putative tumor suppressor gene. In 58% of the tumors displaying LOH, all markers used in this study incurred allele loss. In contrast, retention of heterozygosity was observed at all markers tested in each of the adenomas studied, which suggests that the inactivation of this tumor suppressor gene participates in mouse lung tumor progression.
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PMID:Allelic loss of distal chromosome 4 in mouse lung tumors localize a putative tumor suppressor gene to a region homologous with human chromosome 1p36. 747 9

Genetic changes leading to the development of prostate cancer and factors that underlie the clinical progression of the disease are poorly characterized. Here, we used comparative genomic hybridization (CGH) to screen for DNA sequence copy number changes along all chromosomes in 31 primary and 9 recurrent uncultured prostate carcinomas. The aim of the study was to identify those chromosome regions that contain genes important for the development of prostate cancer and to identify genetic markers of tumor progression. CGH analysis indicated that 74% of primary prostate carcinoma showed DNA sequence copy number changes. Losses were 5 times more common than gains and most often involved 8p (32%), 13q (32%), 6q (22%), 16q (19%), 18q (19%), and 9p (16%). Allelic loss studies with 5 polymorphic microsatellite markers for 4 different chromosomes were done from 13 samples and showed a 76% concordance with CGH results. In local recurrences that developed during endocrine therapy, there were significantly more gains (P < 0.001) and losses (P < 0.05) of DNA sequences than in primary tumors, with gains of 8q (found in 89% of recurrences versus 6% of primary tumors), X (56% versus 0%), and 7 (56% versus 10%), as well as loss of 8p (78% versus 32%), being particularly often involved. In conclusion, our CGH results indicate that losses of several chromosomal regions are common genetic changes in primary tumors, suggesting that deletional inactivation of putative tumor suppressor genes in these chromosomal sites is likely to underlie development of prostate cancer. Furthermore, the pattern of genetic changes seen in recurrent tumors with the frequent gains of 7, 8q, and X suggests that the progression of prostate cancer and development of hormone-independent growth may have a distinct genetic basis. These chromosome aberrations may have diagnostic utility as markers of prostate cancer progression.
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PMID:Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization. 752 34

Although human breast tumorigenesis is associated with the accumulation of mutations both in oncogenes and in tumor suppressor genes, the identity of the genetic alterations that are critical in the early stages of the breast tumorigenic process remains obscure. A high frequency (27-41%) of loss of heterozygosity (LOH) occurrence has been shown at the MET locus on chromosome band 7q31 and this specific alteration is associated with poorer survival. Here, we report that restriction fragment length polymorphism (RFLP) analysis on 221 informative (heterozygous) primary breast tumors and 57 informative relapses (13 local recurrences and 44 distant metastases) revealed a similar frequency of 7q31 LOH as tumors progress from primary cancer to relapse, in marked contrast to other changes such as 11p15.5 LOH. This finding suggests that inactivation of a putative tumor suppressor gene located in 7q31 is a very early event in breast tumorigenesis. Our results also show that metastatic potential is an induced phenomenon that occurs at a relatively early stage, rather than a marker of tumor progression.
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PMID:Loss of heterozygosity on 7q31 occurs early during breast tumorigenesis. 753 86

Recently the putative tumor suppressor gene p16INK4 was mapped to human chromosome 9p21, which is homologous to rat chromosome 5. Monosomy of rat chromosome 5 occurs with high frequency in rat kidney tumor-derived cell lines (ERC lines). Thus, we studied these lines in order to investigate the involvement of p15INK4B and p16INK4 in the genesis of this tumor type. p15INK4B and p16INK4 were found by Southern blot analysis to be codeleted in five of seven of these lines. This was confirmed by Northern blot analysis with a probe for the rat p15INK4B gene. In normal rat tissues, expression of p15INK4B was abundant in lung (2.5 and 2.0 kilobases), less abundant in testis (2.5, 2.0, 1.1, and 0.9 kilobases), barely detectable in liver (2.0 kilobases), and not detectable in neonatal kidney, adult kidney, brain, heart, or spleen. In the ERC lines, p15INK4B was expressed as a single 2.0-kilobase transcript observed only in those cell lines in which the gene was detected by Southern blot analysis. However, neither p15INK4B nor p16INK4 were deleted in 12 of 12 primary kidney tumors examined, suggesting that deletion of these genes is not directly involved in the process of renal tumor development but may be related to tumor progression or autonomous growth in vitro. A panel of rat kidney epithelial cell lines chemically transformed in vitro (TRKE lines) that had high-frequency monosomy 5 were also examined, but deletion of p15INK4B and p16INK4 was observed in only one of six of the TRKE lines. To our knowledge, this is the first reported investigation of these genes in rodent tumors and cell lines, and its data support the theory that alterations of genes located in the INF region of rat chromosome 5 may play a role in rodent cell transformation.
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PMID:Association of rat p15INK4B/p16INK4 deletions with monosomy 5 in kidney epithelial cell lines but not primary renal tumors. 771 60

WHO grades II and III astrocytomas frequently exhibit loss of genetic material on chromosomes 9p, 11p, 17p, 19q, and 22q, indicating that these chromosomal regions harbor tumor suppressor genes involved in the pathogenesis of astrocytic neoplasms. The present study was conducted to examine whether these genetic regions are involved in the process of malignant progression from astrocytoma WHO grade II (A II) to anaplastic astrocytoma WHO grade III (A III). We have analyzed 44 astrocytomas, i.e., 18 A II and 26 A III for loss of heterozygosity (LOH) on chromosomes 1p, 1q, 9p, 9q, 10p, 10q, 11p, 13q, 17p, 19p, 19q, and 22q and for amplification of the epidermal growth factor receptor gene. A polymerase chain reaction-based assay with microsatellite repeat sequences was used for the detection of polymorphisms on silver-stained polyacrylamide gels. LOH on 9p was seen in 1 of 18 (6%) informative cases of A II and 4 of 24 (17%) informative cases of A III. LOH on 17p was observed in 9 of 17 (53%) informative cases of A II and 15 of 26 (58%) informative cases of A III. LOH on 19q was detected in 2 of 18 (11%) informative cases of A II and in 12 of 26 (46%) informative cases of A III. The association of LOH on 19q with anaplasia in astrocytoma was significant (P = 0.015). Amplification of the epidermal growth factor receptor gene was not detected in A II or A III. These data suggest that a putative tumor suppressor gene on the long arm of chromosome 19 is a candidate for a gene associated with tumor progression in astrocytic gliomas.
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PMID:Loci associated with malignant progression in astrocytomas: a candidate on chromosome 19q. 813 36

Reduced expression and/or allelic loss of the putative tumor suppressor gene DCC has been demonstrated in colorectal, gastric, pancreatic, esophageal, breast, and hematological malignancies. We examined the expression of the DCC gene in 22 tissue samples from human gliomas (glioblastoma multiforme, oligodendroglioma, and mixed oligodendroglioma/astrocytoma). Seven of 8 glioblastomas multiforme (88%) had reduced or absent DCC expression, and 8 of the other 14 tumors underexpressed DCC when compared to normal brain tissue. These results demonstrate that reduced expression of DCC occurs in human malignant gliomas and may be part of a common genetic pathway leading to neoplastic transformation and/or tumor progression.
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PMID:Expression of the tumor suppressor gene DCC in human gliomas. 824 11

Hereditary renal carcinoma (RC) in the rat, originally reported by R. Eker in 1954, is an example of a Mendelian dominant predisposition to a specific cancer in an experimental animal. At the histologic level, RCs develop through multiple stages from early preneoplastic lesions (e.g., atypical tubules) to adenomas in virtually all heterozygotes by the age of 1 year. The homozygous mutant condition is lethal at approximately 10 days of fetal life. Ionizing radiation induces additional tumors in a linear dose-response relationship, suggesting that in heterozygotes two events (one inherited, one somatic) are necessary to produce tumors, and that the predisposing gene is a tumor suppressor gene. No genetic linkage has yet been found between the Eker mutation and rat DNA sequences homologous to those in human chromosome 3p, the presumed site of the putative tumor suppressor gene responsible for human RC. Nonrandom loss of rat chromosome 5 in RC-derived cell lines is sometimes associated with homozygous deletion of the interferon gene loci at rat chromosome bands 5q31-q33. Since this locus is not linked with the predisposing inherited gene in the Eker rat, it probably represents a second tumor suppressor gene involved in tumor progression.
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PMID:Spontaneous and radiation-induced renal tumors in the Eker rat model of dominantly inherited cancer. 841 37

FRA3B at human chromosomal band 3p14.2 is the most active common fragile site in the human genome. The molecular mechanism of fragility at this region remains unknown but does not involve expansion of a trinucleotide or minisatellite repeat as has been observed for several of the cloned rare fragile sites. Deletions and rearrangements at FRA3B have been observed in a number of distinct tumors. The recently identified putative tumor suppressor gene FHIT spans FRA3B, and various groups have reported identifying deletions in this gene in different tumors. Using a high density of PCR amplifiable markers within FRA3B searching for deletions in the FRA3B region, we have analysed 21 tumor cell lines derived from renal cell, pancreatic, and ovarian carcinomas. We found a commonly deleted region in the renal cell and ovarian carcinoma cell lines located in the middle of an HPV16 viral integration site. Despite the presence of deletions in the FRA3B region in most of the cell lines, we did not detect alterations in FHIT exons in any of the cell lines examined. Thus, deletions of 3p14.2 in these carcinoma cell lines may simply reflect instability of the FRA3B region during tumor progression.
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PMID:Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact. 948 9

Previous studies have shown that allelic losses in a locus mapping to the chromosomal region 4p14-16 are indicative of poor prognosis in colorectal cancer. To further characterize the region involved and to confirm earlier observations, we have analyzed losses of heterozygosity (LOH) in nine microsatellite markers spanning this region in a prospective series of 181 colorectal carcinomas. The extent and the nature of the allelic imbalance were also ascertained by comparative genomic hybridization analysis of selected cases. The minimum common deleted region was confined to marker D4S2397 (LOH in 35% of the informative cases). Surrounding markers displayed LOH in 13-25% of informative cases and (other than the D4S2397 marker itself) showed a higher rate of allelic imbalances in association with mutations in the p53 tumor suppressor gene. Tumors with lymph node invasion also displayed increased rates of LOH in most markers. Regarding patient outcome, LOH solely at the D4S2397 locus was indicative of a shorter disease-free survival (P = 0.027). In consequence, two patterns of allelic loss are defined within the 4p14-16 region: (a) gross losses associated with tumor progression and probably attributable to the genomic instability related to the inactivation of the p53 tumor suppressor gene; and (b) specific losses limited to the D4S2397 locus (within an estimated fragment of 2 Mb) and associated with increased tumor aggressiveness. The presence of one or more putative tumor suppressor genes in this region is postulated.
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PMID:Prospective assessment of allelic losses at 4p14-16 in colorectal cancer: two mutational patterns and a locus associated with poorer survival. 1058 58


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