Analysis of p53 gene mutations in low- and high-grade astrocytomas by polymerase chain reaction-assisted single-strand conformation polymorphism and immunohistochemistry

Abstract

Using polymerase chain reaction-assisted single-strand conformation polymorphism (PCR-SSCP) and immunohistochemical analyses, mutations in the p53 tumor suppressor gene were examined in 19 low- and high-grade gliomas. By PCR-SSCP and nucleotide analyses, p53 gene mutation was seen in 7 gliomas. Out of the 7 mutations, 3 were located at the CpG site of the previously proposed hot-spot codons 248 and 273, 2 were at codons 171 and 214 and the other 2 were in intron 5, 1 at the splice acceptor site and the other in the vicinity of the splice donor site. The latter 4 mutations have not, or only rarely, been observed in gliomas or in other tumors. However, their effect on the structural and functional alteration of the p53 protein was suggested by positive intranuclear p53 immunostaining in neoplastic cells in 3 mutations including the 1 at the splice acceptor site. In connection with glioma grading, the p53 gene mutation was shown to have occurred in both low- and high-grade gliomas, often in most of the neoplastic cells, as suggested by lack of distinct normal bands and ladders in SSCP and direct sequencing, respectively. The absence of recurrence and malignant transformation over a considerably long postoperative time in our low-grade glioma cases suggested that the p53 gene mutation might not be sufficient for the progression from low- to high-grade gliomas. The frequency of detection of mutation was 7/19(37%) by PCR-SSCP, 8/19(42%) by immunohistochemistry and 10/19(53%) by both methods. The results of PCR-SSCP and immunohistochemistry were consistent in 14 cases (73.7%), but not in 5 cases(26.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic alterations associated with adult diffuse astrocytic tumors

“…Molecular studies performed on anaplastic astrocytomas showed that TP53 mutations occur with approximately the same frequency as in astrocytomas. In addition, the overexpression of PDGF and PDGF receptors and allelic loss on 22q was similar to that observed in astrocytomas, supporting the theory that astrocytomas evolve into anaplastic astrocytomas [James et al, 1988; Fults et al, 1992a; von Deimling et al, 1992a; Louis et al, 1993; Koga et al, 1994; Van Meyel et al, 1994]. Molecular changes that mark the transition from astrocytoma to anaplastic astrocytoma include LOH on 9p, 11p, 13q, and 19q.…”

Genomic difference analysis by two-dimensional DNA fingerprinting reveals typical changes in human low-grade gliomas

“…According to our data, additional genomic changes may trigger astrocytoma growth. It remains to be clarified if these DNA variations will show a relation to prognosis, which could not be demonstrated for mutations of p53 (Koga et al, 1994;Rasheed et al, 1994).…”

Pleomorphic Xanthoastrocytoma With Anaplastic Features- A Rare Case Report and Review of Literature

“…Eighteen cases of PXA showing anaplastic features at the first presentation have been reported in the literature till now. [6,9,10,11,12] In Gianni et al study the significance of the mitotic index, the presence of necrosis and the extent of resection were analysed and found that the mitotic index and the extent of resection were the main predictors for recurrence free survival and overall survival rates. [2] Data to support the role of adjuvant treatment are scanty and sparse.…”

“…In Koga et al case report with institution of stereotactic radiosurgery, survival was prolonged upto 66 months even with multiple nodular dissemination for several times. [10] Macaulay et al [13] addressed the role of adjuvant radiation therapy in these tumours and reported a trend towards better recurrence-free survival with use of adjuvant radiation. However, the difference in overall survival was not statistically significant despite a long follow-up period of fifteen years.…”