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Pilocytic astrocytomas are the most common type of brain tumors in children. Although patients with benign astrocytomas often survive for many years, a significant number will experience recurrent disease. To date, however, little is known about the molecular etiology of histologically benign astrocytomas, and even less about genetic changes associated with tumor recurrence or malignant transformation. Mutations of other components of the RAS pathway were known to be causes of genetic diseases. Further efforts of molecular genetic analyses of pilocytic astrocytomas might lead to a better understanding of the biological behavior of astrocytomas. Objective: aims to identify the underlying genetic defects within the components of the RAS signaling pathway in pilocytic astrocytomas. Methods: 123 DNA samples of pilocytic astrocytomas were screened with DHPLC for mutations of candidate genes BRAF, KRAS, NRAS, MEK1, MEK2 and PTPN11. Samples with an abnormal DHPLC-profile were selected to be sequenced for detection of mutation. Results: Mutational analysis of candidate genes of the RAS signaling pathway in 123 tumor samples of pilocytic astrocytomas detected mutational rates: 8.13% of BRAF exon 15 (p.V600E, Y599Ins), 0.81% of KRAS exon 3 (p.E63K), 0.81% of MEK2 exon 7 (p.R238Q). Furthermore, the present study also revealed the polymorphism rates: 3.2% of NRAS exon 2, 1.62% of MEK2 exon 2; and intronic alternation: 3.2% of MEK1 exon 2 (IVS2+22), 0.81% of MEK2 exon 2 (IVS2+18). The point mutations of KRAS exon 3 and MEK2 gene exon 7, which were detected in our study, have not been reported previously in pilocytic astrocytomas. Conclusions: somatic mutations in different components of the RAS signaling pathway played a role in the formation of pilocytic astrocytomas.

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