Oligodendroglioma - Deletion 1p / 19q
Gliomas are a group of benign and malignant neoplasms of the central nervous system derived from glial cells (astrocytes, oligodendrocytes and ependymal cells). Astrocytes result astrocytomas or glioblastoma multiforme; oligodendrocytes result in oligodendrogliomas; and ependymal cells give rise to epedimomomas, neoplasms of the choroid plexus, or colloid cysts of the third ventricle. In these tumors they have been investigated genetic alterations that confer increased susceptibility to develop. These genetic alterations found in several genes, which confer greater predisposition or facilitate the development of these tumors, are considered "oncogenes". Of these, the most studied are PTEN (Phosphatase and tensin homolog), the DMBT1 gene (Brain Tumors Malignant delected in 1) and TP53. Other genes that have been implicated are: GLM4, GLM5, GLM6, GLM7, GLM8, ERBB, ERBB2, LG11, GAS41 Idh1, IDH2, BRAF, PARK2, EGFR, and CDKN2A. Logically, the study of genetic alterations of these genes of interest to know the predisposition for the development and pathogenesis of these tumors.
However, once diagnosed one of these tumors, and characterized histologically, according to its cellular composition have been studied other genetic markers that could explain the different types of evolution were observed between tumor that were similar from Histologically .
The molecular alterations best characterized in oligodendrogliomas, and that explain the differences in therapeutic response with antineoplastic drugs, probability of recurrence after therapeutic response, and serving thus to establish a prognosis, are the deletion found in the arm short of chromosome 1 (1p), and the long arm of chromosome 19 (19q). Both together correspond to the deletion 1p / 19q. In these regions there are tumor suppressor genes and / or genes of DNA repair charge, whose inactivation may lead to these tumors. These alterations (deletions) are in the 60 to 85% of them.
Loss of 1p / 19q in oligodendrogliomas are proven to be associated with a better response to chemotherapy and is associated with a higher survival rate. Based on the presence of said deletion, oligodendrogliomas have been subdivided into three groups with therapeutic relevance: 1) those oligodendrogliomas possessing only loss by deletion of 1p / 19q, which have a response to the relevant and lasting chemotherapy related prolonged survival, with or without postoperative radiation; 2) those with deletion of 1p loss and TP53 mutation in the gene (exons 5 to 8) responsive to chemotherapy but that turn in a short time; and 3) those with deletion of 1p loss but without mutations in the TP53 gene, with poor prognosis, very aggressive, like glioblastomas.
Tests in IVAMI: in IVAMI perform detection 1p deletions and 19q by the technique of quantitative analysis of microsatellite PCR in real time, considering 10 (ten) microsatellites of chromosome 1, 6 (six) microsatellites of chromosome 19, and 6 (six) microsatellite other chromosomes as control (chromosomes 2, 3, 5, 8, 12 and / or 21). MLPA not perform the procedures (Multiple Ligation dependent Probe Amplification), or FISH (Fluorescent in situ Hybridization), by using commercial kits or loss of heterozygosity (LOH: Lost of hetogozygosity), not to provide additional information.
Recommended samples: 1) Sample of tumor biopsy, preserved or frozen cut paraffin embedded biopsy: two samples are needed. Is necessary microdissection of tumor tissue to seek only tumor tissue, avoiding taking normal tissue; and 2) peripheral blood collected with EDTA to remove leukocytes, intended for use as a normal cellular control patient.