Amplified DNA in Y1 mouse adrenal tumor cells: isolation of cDNAs complementary to an amplified c-Ki-<i>ras</i>gene and localization of homologous sequences to mouse chromosome 6

George, Donna L.; Scott, Alan F.; Martinville, B de; Francke, Uta

doi:10.1093/nar/12.6.2731

Cited by 29 publications

(11 citation statements)

References 34 publications

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“…Over-expression of K-ras mRNA occurs in approximately 37.5% (6 of 16 cases tested) of functional adrenocortical adenomas and predominantly occurred with the presence of mutations in the K-ras gene. This phenomenon was also found in mouse adrenocortical tumour cells (Schwab et al, 1983;George et al 1984;George et al, 1985). The phenomenon of over-expression of K-ras mRNA has been investigated by Schwab et al (1993) in mouse models.…”

Section: Discussionmentioning

confidence: 68%

Mutations of K-ras oncogene in human adrenal tumours in Taiwan

Lin

Tsai²,

Yang³

et al. 1998

Br J Cancer

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Summary Recently, we have found a high frequency of p53 gene mutations in human functional adrenal tumours. As the tumorigenesis is a multigene defect, we believe that other oncogenes may also be involved in the initiation or progression of adrenal tumours. Using the singlestrand conformational polymorphism (SSCP) method, we chose the ras oncogenes as the target in this screening procedure because their high mutation rates were detected in thyroid tumours. For the ras oncogenes analysed, exon 1 to exon 2 of H-ras and K-ras genes in the tumour tissues of 13 Conn's syndrome, two adrenal Cushing's syndrome, two non-functional adrenal tumours, one adrenocortical hyperplasia and eight phaeochromocytomas and its paired adjacent normal adrenal tissues were amplified and sequenced. No mutations were detected in the H-ras gene. But mutations of the K-ras gene were detected in 46% (6 of 13) of Conn's syndrome; the hot spots were located at codon 15, 16, 18 and 31, which were different from those previously found in other tumours (codon 12, 13 and 61). Northern blot analysis with 1.1 kb K-ras cDNA revealed that K-ras mRNA was more than tenfold over-expressed in four of Conn's syndrome, one case of Cushing's syndrome and one case of adrenocortical hyperplasia. The mutation sites and mutation type were not found in other tissues, which confered that this was highly related to adrenocortical tumours. Yet, the correlation between K-ras oncogene and adrenocortical tumours needs to be clarified by further studies.

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Section: Discussionmentioning

confidence: 68%

Mutations of K-ras oncogene in human adrenal tumours in Taiwan

Lin

Tsai²,

Yang³

et al. 1998

Br J Cancer

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“…Oncogenes may be present in these amplicons, the most characteristic example being the MYCN gene in neuroblastomas. Gene amplification may be detected at the cytogenetic level either extrachromosomally, as double minute chromosomes (DMs) (small, dot-like chromosome masses that can contain thousands of copies of an oncogene 24 ) or intrachromosomally as homogeneously staining regions (HSRs) that are frequently integrated in abnormal chromosomes. 25 In the present study, we first examined eight CNC tumours by CGH, a technique that allows the detection of large changes in tumour DNA (table 1).…”

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confidence: 99%

Chromosome 2 (2p16) abnormalities in Carney complex tumours

Matyakhina

Pack²,

Kirschner³

et al. 2003

Journal of Medical Genetics

120

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Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia and lentiginosis syndrome characterised by spotty skin pigmentation, cardiac, skin, and breast myxomas, and a variety of endocrine and other tumours. The disease is genetically heterogeneous; two loci have been mapped to chromosomes 17q22-24 (the CNC1 locus) and 2p16 (CNC2). Mutations in the PRKAR1A tumour suppressor gene were recently found in CNC1 mapping kindreds, while the CNC2 and perhaps other genes remain unidentified. Analysis of tumour chromosome rearrangements is a useful tool for uncovering genes with a role in tumorigenesis and/or tumour progression. CGH analysis showed a low level 2p amplification recurrently in four of eight CNC tumours; one tumour showed specific amplification of the 2p16-p23 region only. To define more precisely the 2p amplicon in these and other tumours, we completed the genomic mapping of the CNC2 region, and analysed 46 tumour samples from CNC patients with and without PRKAR1A mutations by fluorescence in situ hybridisation (FISH) using bacterial artificial chromosomes (BACs). Consistent cytogenetic changes of the region were detected in 40 (87%) of the samples analysed. Twenty-four samples (60%) showed amplification of the region represented as homogeneously stained regions (HSRs). The size of the amplicon varied from case to case, and frequently from cell to cell in the same tumour. Three tumours (8%) showed both amplification and deletion of the region in their cells. Thirteen tumours (32%) showed deletions only. These molecular cytogenetic changes included the region that is covered by BACs 400-P-14 and 514-O-11 and, in the genetic map, corresponds to an area flanked by polymorphic markers D2S2251 and D2S2292; other BACs on the centromeric and telomeric end of this region were included in varying degrees. We conclude that cytogenetic changes of the 2p16 chromosomal region that harbours the CNC2 locus are frequently observed in tumours from CNC patients, including those with germline, inactivating PRKAR1A mutations. These changes are mostly amplifications of the 2p16 region, that overlap with a previously identified amplicon in sporadic thyroid cancer, and an area often deleted in sporadic adrenal tumours. Both thyroid and adrenal tumours constitute part of CNC indicating that the responsible gene(s) in this area may indeed be involved in both inherited and sporadic endocrine tumour pathogenesis and/or progression.

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“…An elevated copy number (30-to 60-fold) of the KRAS2 amplicon in human malignancy, suggesting that gene has also been observed in the murine adrenal either may contribute to the malignant phenotype. carcinoma cell line Y1 (George et al, 1984). Differential…”

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confidence: 99%