Chromosome 9 related aberrations and deletions of the CDKN2 and MTS2 putative tumor suppressor genes in human chondrosareomas

Jagasia, Ashok A.; Block, Joel A.; Qureshi, Abid; Dı́az, Manuel O.; Gitelis, Steven; Iyer, Anand

doi:10.1016/0304-3835(96)04274-7

Cited by 49 publications

(30 citation statements)

References 31 publications

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“…Previous studies, restricted to either one or two of these components, have indicated that this pathway may be of interest in chondrosarcoma [1, 17,18,27]. In this study, alterations in p16, pl?b and cdk4 were seen both at the protein and the DNA level.…”

Section: Discussionsupporting

confidence: 58%

“…To find out if alterations in this pathway could be useful in an alternative grading system in this tumor group, we analyzed the occurrence of p16, pRb and cdk4 in cultured cells from eight chondrosarcomas and in two chondrosarcoma cell lines. Since previous studies on chondrosarcoina cell lines have shown cytogenetic abnormalities of chromosome 9 where CDKN2 is located and in addition partial deletion of the gene [17,18] we also extended the present study to search for genetic alterations of CDKN2.…”

Section: J Asp Et Ul I Journal Of Orthopaedic Rejeuvch 19 (2001) 149-154mentioning

confidence: 86%

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Alterations in the regulatory pathway involving p16, pRb and cdk4 in human chondrosarcoma

Asp

Inerot

Block

et al. 2001

Journal Orthopaedic Research

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The G1 regulatory pathway involving p16, pRb and cdk4 in the cell cycle has been investigated in human chondrosarcoma. The protein expression of p16, pRb and cdk4 was analyzed by Western blot in cultured cells from eight chondrosarcomas and in two chondrosarcoma cell lines. Both cell lines and one other sample were negative for p16. Moreover, one of the cell lines w d S pRbnegative and showed a high expression of cdk4 as well. In the other cell line and in three other samples pRb of expected size were detected in addition to a shorter form of the protein. To further investigate the reasons for down-regulation of the p16 protein, the pl6-coding gene CDRN2 was analyzed by polymerase chain reaction (PCR), methyl-specific PCR (MSP) and sequencing in all tumor samples as well as in corresponding tumor tissues from three of the samples. The pl6-negative samples were all found to have homozygous deletion of CDKN2. Another sample showed partial gene methylation and a heterozygous position in codon 148 was detected in one sample. The same base substitution was also found in two of the tissue samples. Finally, cytogenetic analysis of the samples with homozygously deleted CDKN? revealed multiple structural abnormalities in all three cases. In conclusion, the p161 pRbkdk4 pathway may play an important role in the pathogenesis of some chondrosarcomas.

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Section: Discussionsupporting

confidence: 58%

Section: J Asp Et Ul I Journal Of Orthopaedic Rejeuvch 19 (2001) 149-154mentioning

confidence: 86%

Alterations in the regulatory pathway involving p16, pRb and cdk4 in human chondrosarcoma

Asp

Inerot

Block

et al. 2001

Journal Orthopaedic Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Numerous studies in chondrosarcomas (Jagasia et al, 1996), skin cancers (Holmberg et al, 1996), lung carcinomas (Wiest et al, 1997), neuroblastomas (Marshall et al, 1997), breast carcinomas (Gorgoulis et al, 1998), sporadic basal cell carcinomas (He et al, 1999), cutaneous malignant melanomas (Parris et al, 1999), bladder cancers , renal cell carcinomas (Grady et al, 2001), and ESCC (Nishiwaki et al, 2000) have suggested that chromosome 9 may harbor several other TSGs besides p16INK4a. Tumor suppression using MMCT helps narrow down the search for key genes contributing to tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Tumor suppressive role of a 2.4 Mb 9q33–q34 critical region and DEC1 in esophageal squamous cell carcinoma

Yang

Leung

et al. 2004

Oncogene

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The key genes involved in the development of esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Previous studies indicate extensive genomic alterations occur on chromosome 9 in ESCC. Using a monochromosome transfer approach, this study provides functional evidence and narrows down the critical region (CR) responsible for chromosome 9 tumor suppressing activity to a 2.4 Mb region mapping to 9q33-q34 between markers D9S1798 and D9S61. Interestingly, a high prevalence of allelic loss in this CR is also observed in primary ESCC tumors by microsatellite typing. Allelic loss is found in 30/ 34 (88%) tumors and the loss of heterozygosity (LOH) frequency ranges from 67 to 86%. Absent to low expression of a 9q32 candidate tumor suppressor gene (TSG), DEC1 (deleted in esophageal cancer 1), is detected in four Asian ESCC cell lines. Stably expressing DEC1 transfectants provide functional evidence for inhibition of tumor growth in nude mice and DEC1 expression is decreased in tumor segregants arising after long-term selection in vivo. There is 74% LOH in the DEC1 region of ESCC primary tumors. This study provides the first functional evidence for the presence of critical tumor suppressive regions on 9q33-q34. DEC1 is a candidate TSG that may be involved in ESCC development.

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“…16 Alterations of putative tumor suppressor genes (CDKN2 and MTS-2) located on chromosome 9 were identified in chondrosarcoma cell lines. 17 Amplification of the cmyc protooncogene without any apparent correlation to histologic grade was found in another small series of chondrosarcoma cases. 18 More recently, evidence of frequent loss of heterozygosity on 17p and the presence of multiple chromosomal alterations were correlated with high histologic grade 19 -23 and aggressive clinical behavior 21 in a few small series of chondrosarcoma of bone.…”

mentioning

confidence: 99%

Altered p53 is associated with aggressive behavior of chondrosarcoma

Oshiro

Chaturvedi

Hayden

et al. 1998

Cancer

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Chromosome 9 related aberrations and deletions of the CDKN2 and MTS2 putative tumor suppressor genes in human chondrosareomas

Cited by 49 publications

References 31 publications

Alterations in the regulatory pathway involving p16, pRb and cdk4 in human chondrosarcoma

Alterations in the regulatory pathway involving p16, pRb and cdk4 in human chondrosarcoma

Tumor suppressive role of a 2.4 Mb 9q33–q34 critical region and DEC1 in esophageal squamous cell carcinoma

Altered p53 is associated with aggressive behavior of chondrosarcoma

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