No correlation of c- myc overexpression and p53 mutations in liposarcomas

Abstract

Although it is well known that oncogenesis is a multistep process involving the activation of normal cellular genes to become oncogenes and/or the inactivation of tumor suppressor genes, this process has seldom been investigated in soft tissue tumours. We screened a group of 36 liposarcomas for genetic abnormalities in the p53 tumour suppressor gene and c-myc oncogene. Altered c-myc gene expression was examined by differential RT-PCR assay. p53 Gene mutations in exons 4-8 were analysed by using PCR-SSCP analysis and direct sequencing. Elevated c-myc expression was found in 6 of 31 liposarcomas (19.4%). p53 Gene mutations were observed in 5 of 36 liposarcomas (13.9%). Both genetic alterations were associated with the histological subtype of liposarcomas. Whereas c-myc gene expression was a characteristic of myxoid/round cell liposarcomas, p53 gene mutations were found more frequently in pleomorphic variants. Liposarcomas of the well-differentiated subtype showed neither p53 gene mutations nor altered c-myc gene expression. Our results indicate that the c-myc oncogene and the p53 tumor suppressor gene do not seem to cooperate in the oncogenesis of liposarcomas.

Prognostic significance of p53 gene mutations and p53 protein expression in synovial sarcomas

“…This mutation frequency is lower than that observed in other soft tissue sarcoma entities (leiomyosarcomas: 20% [23,29], 16% [7]; malignant schwannomas: 33%, MFHs: 21% [24]; liposarcomas: 13% [8,26,27], 15% [30], 7% [31]). To date, according to the p53 data bank of Hainaut et al [14], there are no records on p53 mutations in synovial sarcoma.…”

Prognostic Significance of Nuclear Accumulation of c-myc and mdm2 Proteins in Synovial Sarcoma of the Extremities

“…Moreover, the demonstration that experimental suppression of amplified MYC genes from human tumour cells is associated with loss of tumorigenicity [28]suggests its involvement in tumour aggressiveness. Although amplification or enhanced expression of C-MYC have been detected in several tumours, including sarcomas [3, 25, 29, 30, 31], the significance of C-MYC over…”

“…Since amplification of C-MYC or MDM2 genes is not invariably associated with overproduction of their corresponding mRNA, increased levels of these proteins without gene amplification or overexpression being much more common than the opposite [21, 22, 23, 24, 25, 26], we used immunohistochemistry for assessment of nuclear accumulation of c-myc or mdm2 proteins in a homogeneous series of patients with primary, nonmetastatic synovial sarcomas of the extremities.…”

High telomerase activity and high HTRT mRNA expression differentiate pure myxoid and myxoid/round-cell liposarcomas

“…Amplification was performed in an automated thermal cycler (Multicycler PTC 200; MJ Research, Watertown, MA) for 31 cycles (hTRT) and 28 cycles (hTR), at 94°C for 45 sec, 60°C for 45 sec and 72°C for 90 sec, followed by a final extension step at 72°C for 10 min. ␤2-microglobulin (␤2-M) mRNA was amplified to normalize equal amounts of RNA template using the primers and PCR conditions described by Schneider-Stock et al (1998b). A negative control reaction without cDNA was included in each experiment.…”

“…Although TP53 mutations, CDK4/CDK6 expression and RB1 and TP53 losses were common, these genetic changes were independent of the histological grade of the tumor (Dei Tos et al, 1997;Schneider-Stock et al, 1998a). However, there was a correlation between high-grade round-cell morphology and higher c-MYCexpression level (Schneider-Stock et al, 1998b) and MDM2 protein expression (Dei Tos et al, 1997), respectively, reflecting a possible correlation with tumor progression.…”