Nonrandom duplication of the chromosome bearing a mutated Ha-ras-1 allele in mouse skin tumors.

Bianchi, A.; Aldaz, C. Marcelo; Conti, Claudio J.

doi:10.1073/pnas.87.17.6902

Cited by 88 publications

(68 citation statements)

References 27 publications

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“…This is the time when these tumors become dysplastic and develop chromosomal numerical abnormalities (Aldaz et al, 1987). We speculate that the changes observed in the expression of cell-cycle proteins are connected with the histopathologic changes and chromosomal alterations observed in this model (Aldaz et al, 1987(Aldaz et al, , 1989Bianchi et al, 1990).…”

Section: Discussionmentioning

confidence: 65%

“…Important changes occur at 20 weeks, when most of the papillomas became moderately dysplastic and atypical cells appear in the basal and suprabasal layers, and at 30 ± 40 weeks, the papillomas are severely dysplastic (Aldaz et al, 1987). Concomitant with the histologic changes, papilloma progression results in chromosomal numerical alterations with non-random trisomization in chromosomes 6 and 7 (Aldaz et al, 1989;Bianchi et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

et al. 1998

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It is now evident that several genes encoding regulatory activities that control the mammalian cell cycle, particularly some that control the progression of quiescent cells through G1 and into S phase, are targets for alterations that underlie the development of neoplasms. Here, we made a sequential study of alterations in cell cycle protein expression and complex formation among cyclin, cyclin dependent kinases (CDKs) and CDK inhibitors (CKIs) during premalignant progression in SENCAR mouse skin tumors. Changes in the level of expression were observed in positive (cyclin D1, D2, and E2F family members) and negative regulators (p16 Ink4a , p57 Kip2 ) of the cell cycle. Also, we observed the formation of cyclin/CDK/CKI complexes. The amounts of these proteins and complexes increased substantially at speci®c times during promotion but not during malignant conversion to carcinomas. These data show that deregulation of growth control occurs in benign tumors and that subsequent mutations not involved cell-cycle regulation are probably necessary to induce invasive behavior.

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Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

et al. 1998

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“…A transition in codon 12 of Hras [Brown et al, 1990]. Subsequent nonrandom duplication of the chromosomal region spanning the Hras locus results in an increased copy number of activated Ras [Bianchi et al, 1990], followed by loss of the normal Hras allele [Bremner and Balmain, 1990]. We speculate that a similar progression occurred in the ERMS with the primary tumor demonstrating chromosome 11 trisomy, and then subsequent loss of wild-type HRAS in the recurrent malignancy.…”

Section: Discussionmentioning

confidence: 83%

HRAS mutations in Costello syndrome: Detection of constitutional activating mutations in codon 12 and 13 and loss of wild‐type allele in malignancy

Estep

Tidyman

Teitell

et al. 2005

American J of Med Genetics Pt A

172

157

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Costello syndrome (CS) is a complex developmental disorder involving characteristic craniofacial features, failure to thrive, developmental delay, cardiac and skeletal anomalies, and a predisposition to develop neoplasia. Based on similarities with other cancer syndromes, we previously hypothesized that CS is likely due to activation of signal transduction through the Ras/MAPK pathway [Tartaglia et al., 2003]. In this study, the HRAS coding region was sequenced for mutations in a large, well‐characterized cohort of 36 CS patients. Heterogeneous missense point mutations predicting an amino acid substitution were identified in 33/36 (92%) patients. The majority (91%) had a 34G → A transition in codon 12. Less frequent mutations included 35G → C (codon 12) and 37G → T (codon 13). Parental samples did not have an HRAS mutation supporting the hypothesis of de novo heterogeneous mutations. There is phenotypic variability among patients with a 34G → A transition. The most consistent features included characteristic facies and skin, failure to thrive, developmental delay, musculoskeletal abnormalities, visual impairment, cardiac abnormalities, and generalized hyperpigmentation. The two patients with 35G → C had cardiac arrhythmias whereas one patient with a 37G → T transversion had an enlarged aortic root. Of the patients with a clinical diagnosis of CS, neoplasia was the most consistent phenotypic feature for predicating an HRAS mutation. To gain an understanding of the relationship between constitutional HRAS mutations and malignancy, HRAS was sequenced in an advanced biphasic rhabdomyosarcoma/fibrosarcoma from an individual with a 34G → A mutation. Loss of the wild‐type HRAS allele was observed, suggesting tumorigenesis in CS patients is accompanied by additional somatic changes affecting HRAS. Finally, due to phenotypic overlap between CS and cardio‐facio‐cutaneuos (CFC) syndromes, the HRAS coding region was sequenced in a well‐characterized CFC cohort. No mutations were found which support a distinct genetic etiology between CS and CFC syndromes. © 2005 Wiley‐Liss, Inc.

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“…The deletion of the MET locus on chromosome 7, as demonstrated by FISH data in the patient with a missense mutation (Case 3), may suggest the exclusive expression of the mutant allele by overrepresentation of the mutant allele (30) or loss of suppression effect of the wild-type allele, as shown in defective serine/threonine kinase gene (31).…”

Section: Discussionmentioning

confidence: 97%

Missense Mutation of the MET Gene Detected in Human Glioma

et al. 2000

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Nonrandom duplication of the chromosome bearing a mutated Ha-ras-1 allele in mouse skin tumors.

Cited by 88 publications

References 27 publications

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

HRAS mutations in Costello syndrome: Detection of constitutional activating mutations in codon 12 and 13 and loss of wild‐type allele in malignancy

Missense Mutation of the MET Gene Detected in Human Glioma

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