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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper presents a cytogenetic analysis of two established but early-passage (passages 5 and 18) cell lines derived from histologically similar, poorly differentiated lymph node metastases of squamous cell carcinoma of the lung. The cell lines showed 3 shared marker chromosomes, del(1)(q11), del(2)(p11.1) and del(2)(q11.1). One of the lines (DLKP) had 8 additional markers including structural rearrangements such as translocations and isochromosomes. Five additional markers (including two deletions of chromosome 3) were found in DLRP. A notable feature of DLRP was the high incidence of telomeric association evident in the majority of metaphase plates. Over-representation of chromosome 7 was a characteristic feature of metaphases derived from DLKP, and identification of i(21q) in this cell line was an unusual finding. The results indicate significant cytogenetic heterogeneity between these early-passage cell lines derived from two apparently histologically similar tumors.
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PMID:Cytogenetic comparison of two poorly differentiated human lung squamous cell carcinoma lines. 158 77

Recent linkage of the gene for multiple endocrine neoplasia type 2A and 2B to the centromeric region of chromosome 10 has provided new insight into the causes of medullary thyroid carcinoma and has provided tools to diagnose gene carriers status for this syndrome with greater than 90% certainty. This review focuses on how these advances influence the clinical management of both sporadic and hereditary medullary thyroid carcinoma and discusses how tests based on the genetic linkage studies will aid in the early diagnosis and treatment of this syndrome. In addition, the authors have focused on several controversial management questions regarding the type and extent of surgery for this thyroid tumor, the management of the patient with metastatic disease, and the approach to management of other manifestations of multiple endocrine neoplasia types 2A and 2B. This review attempts to provide a balanced overview of these complex issues.
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PMID:Changing concepts in the management of hereditary and sporadic medullary thyroid carcinoma. 197 73

Malignant fibrous histiocytomas (MFH) often have complex karyotypic abnormalities. Recently, we described a 19p+ marker chromosome in 9 of 22 MFH. Other recurrent karyotypic features have been telomeric associations, ring chromosomes, and structural rearrangements of chromosomal bands 1q11, 3p12, and 11p11. After a median follow-up time of 18 months, distant metastases and/or local recurrence have occurred in 8 of the 9 patients with 19p+ markers but in only 4 of the 13 patients without. The only other cytogenetic parameter that seemed to affect relapse tendency was the presence of ring markers: relapse has occurred in 2 of 8 patients with unidentifiable supernumerary ring marker chromosomes compared to 10 of 14 patients without. No differences in relapse frequency were apparent for tumors belonging to the other cytogenetic subgroups. It thus appears that 19p+ marker chromosomes in MFH signal an increased relapse risk whereas the finding of ring markers indicates a reduced relapse risk.
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PMID:Malignant fibrous histiocytomas with a 19p+ marker chromosome have increased relapse rate. 217 42

Although the incidence of cancer of the esophagus is low in the United States, the prognosis of patients with this malignancy is poor, especially when metastases exist. More research concerning the biological characteristics of this tumor is necessary to permit more effective treatment and to determine the etiology. We successfully studied cytogenetically 14 short- and long-term cell lines derived from esophageal carcinoma to determine whether these tumors have nonrandom, unique chromosomal abnormalities. Our results showed that the tumor cells had chromosome numbers clustering around a modal number that varied according to the cell line. The presence in the primary explant of extensive numerical and structural abnormalities involving every chromosome including the sex chromosomes indicate that these abnormalities occur early in the malignant cells. The chromosomes most frequently involved in the structural abnormalities were 1, 9, and 11, each occurring in 13 of the 14 lines, and of three found in 12 of the 14 lines. The major aberrations resulted in deletions of portions of these chromosomes. The most frequent breakpoints for these abnormalities occurred at 3p14, 11q11q12; and 9q11q12 as well as in the centromeric regions of all the acrocentric chromosomes. Another unusual chromosomal marker found in three lines (HCE-1, HCE-3, and HCE-5) was a homogeneously staining region (HSR) that occurred as an extension on 11q12.
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PMID:Cytogenetic studies of esophageal carcinoma cell lines. 230 77

Fifty-one randomly selected primary squamous cell carcinomas of the head and neck, derived from the larynx (n = 18) and pharynx (oropharynx, n = 18, and hypopharynx, n = 15) were analyzed with centromeric probes for chromosomes 1, 7, 9, 11, 17, and 18 to study numerical aberrations, chromosome imbalances, and aneuploidy by fluorescence in situ hybridization. The tumors were grouped into nonmetastasizing (N0) tumors (from patients clinically free of lymph node metastases for at least 18 months after surgery, n = 25) and metastasizing (N1-3) tumors (n = 26). We found a significant association between the tumor ploidy and the nodal status; in the N0 group, diploidy prevailed, and the most common aberration was loss to monosomy for chromosome 9 (44%), whereas in the N1-3 group, aneuploidy predominated (P = 0.002). Specifically, these genomic changes associated with progression to metastasis were: (a) tetrasomic or polysomic chromosomes were detected in 17 of 26 N1-3 tumors but in none of the 25 N0 tumors (P < 0.0001); (b) heterogeneous chromosomal copy numbers (i.e., extensive chromosomal imbalances) were also much more frequent in the N1-3 tumors (69.2% versus 24.0% in the N0 group; P = 0.018); and (c) loss of chromosome 9 (73%) and gains of chromosomes 7 (35%) and 17 (31%) persisted, but in addition, loss of chromosome 18 occurred in 31%. Overexpression of the p53 protein correlated with an increased incidence of chromosomal imbalances and aneuploidy (P < 0.001) and, hence, constituted an additional risk factor. The lower metastatic potential of larynx tumors as compared with tumors from the pharynx was reflected by a lower incidence of these genomic changes. These specific patterns of chromosomal aberrations can characterize and distinguish different stages of tumor progression of squamous cell carcinomas of the head and neck and should be valuable diagnostic and prognostic markers.
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PMID:Distinct nonrandom patterns of chromosomal aberrations in the progression of squamous cell carcinomas of the head and neck. 758 47

Cells heterozygous for mutations in p53 demonstrate extreme genomic instability and develop mutations detectable at the chromosome level as well as the molecular level. This genomic instability causes initially nontumorigenic ras-expressing immortal LFS cells to progress to a tumorigenic state presumably due to additional mutational events. It is not surprising that LFS families with these p53 mutations develop the additional mutations necessary for cancer to occur at such high frequencies. This observation is consistent with increased cancer rates in these families being due to abrogation of a rate limiting step rather than a rate expected for one less step in a multistep carcinogenic process. Although p53 has been shown to be able to function as a transcription factor, mutations in p53 appear to affect genomic stability in LFS fibroblasts with double minutes and telomeric associations being prominent early events. One possibility is that p53 controls the expression of genes required for fidelity of replication or telomerase activity. Alternatively p53 may itself be a replication factor like the transcription factor CTF. In the future, we plan to investigate whether p53 plays a direct role in replication.
Cancer Metastasis Rev 1995 Mar
PMID:Genomic instability due to germline p53 mutations drives preneoplastic progression toward cancer in human cells. 760 20

Multiple endocrine neoplasia type 1 (MEN 1) is an inherited disease of the neuroendocrine cell system affecting primarily the parathyroids, pancreas, duodenum and the anterior pituitary. The pancreatic and duodenal tumours may metastasize, but generally have a low malignant potential. The diagnosis of MEN 1 is usually made in the second decade of life and based on the involvement of at least two organs and a family history. The recent discovery of the MEN 1 locus on the centromeric region of the long arm of chromosome 11 may become a further diagnostic criterion. The use of flanking DNA markers permits presymptomatic testing for MEN 1 in affected families.
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PMID:Multiple endocrine neoplasia type 1 (MEN 1) revisited. 765 33

Mice bearing retinoblastoma susceptibility gene (RB) germ-line mutations almost invariably develop pituitary neoplasms. We therefore tested 17 patients with pituitary tumors for loss of heterozygosity (LOH) using an RB sequence polymorphism and 5 polymorphic microsatellite markers surrounding the RB gene on the long arm of chromosome 13. In all of the 13 malignant or highly invasive pituitary tumor cases, and in 4 of their respective metastases, a RB allele was lost. In contrast, no LOH at the RB locus was detected in 4 benign pituitary adenoma cases. Three invasive tumors also lost a portion of 13q, which included D13s137, D13s133, and D13s118 telomeric and centromeric to RB, respectively. Immunohistochemical analysis, however, revealed the presence of RB protein in tumors with LOH and the RB locus. Therefore, although inactivation of RB may play a role in the development of invasive pituitary adenomas and carcinomas in mice, another tumor suppressor gene on 13q is likely involved in human pituitary tumor progression. LOH of 13q markers may also be of predictive value in determining the biological behavior of pituitary macroadenomas and their progression to invasiveness and frank malignancy.
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PMID:Frequent loss of heterozygosity at the retinoblastoma susceptibility gene (RB) locus in aggressive pituitary tumors: evidence for a chromosome 13 tumor suppressor gene other than RB. 2886 62

Alterations of the p53 gene are among the most frequent genetic lesions in a variety of human malignancies. Their role in prostate cancer is, however, unclear. We have analyzed 10 primary and two metastatic human prostate carcinomas as well as 3 prostate cancer cell lines for mutations of the p53-gene. Using single strand conformational polymorphism analysis (SSCP) and direct sequencing of the polymerase chain reaction (PCR) products, p53 mutations were detected in 1 of 10 primary prostate cancers. By contrast, 1 of 2 metastatic tumors and all 3 prostate cancer cell lines (derived from metastases) were found to contain a mutant p53 gene. Thus, our data suggest that alterations of the p53 gene at the mutational "hot spots" appear to occur infrequently in primary human prostate cancer, but may emerge in later stages of tumor progression. Furthermore, we confirm that loss of heterozygosity at a locus telomeric to p53, but not including p53, is associated with metastatic progression in 1 case.
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PMID:p53 gene alterations in human prostate carcinoma. 851 Feb 67

Telomeres, the extreme ends of chromosomes, play an important role in chromosome structure and function. The shortening of telomeres is one of the supposed mechanisms of cellular aging and death. Because of end replication problems the length of telomeres decreases with every cell cycle. This may lead to chromosome instability and additional genetic alterations possibly responsible of significant tumor development. In many cancer cells the length of telomeres depends on a balance between the loss of telomeric repeats, at each replication cycle, and the telomere lengthening, by the enzyme telomerase, which is repressed in most normal somatic cells. Many tumor cells demonstrate shortened telomeres in comparison to the corresponding normal tissue. In some types of human cancers the reduction of telomeric repeats was correlated with increasing disease severity. We analyzed Southern blots of HINF1-digested DNA of a large number of renal cell carcinomas (RCC) including different tumor areas, secondary tumors and metastases (76 cases with 142 tumor samples) for changes in the length of telomeric repeats using the oligonucleotide probe (TTAGGG)3 and found telomere shortening in 54%, suggesting that a reduction of the telomeric repeat length is not a general characteristic in RCC. Intratumor heterogeneity was demonstrated in seven cases. But also two RCC, with elongated telomeres in the tumor tissue, were observed. Shortened telomeres do not seem to be associated with advanced stages of tumor development or specific histopathological subtypes of RCC.
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PMID:Changes in telomere lengths in renal cell carcinomas. 882 3


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