Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients

Abstract

Glioblastoma is the most frequent and malignant human brain tumor. High level of genomic instability detected in glioma cells implies that numerous genetic alterations accumulate during glioma pathogenesis. We investigated alterations in AP-PCR DNA profiles of 30 glioma patients, and detected specific changes in 11 genes not previously associated with this disease: LHFPL3, SGCG, HTR4, ITGB1, CPS1, PROS1, GP2, KCNG2, PDE4D, KIR3DL3, and INPP5A. Further correlations revealed that 8 genes might play important role in pathogenesis of glial tumors, while changes in GP2, KCNG2 and KIR3DL3 should be considered as passenger mutations, consequence of high level of genomic instability. Identified genes have a significant role in signal transduction or cell adhesion, which are important processes for cancer development and progression. According to our results, LHFPL3 might be characteristic of primary glioblastoma, SGCG, HTR4, ITGB1, CPS1, PROS1 and INPP5A were detected predominantly in anaplastic astrocytoma, suggesting their role in progression of secondary glioblastoma, while alterations of PDE4D seem to have important role in development of both glioblastoma subtypes. Some of the identified genes showed significant association with p53, p16, and EGFR, but there was no significant correlation between loss of PTEN and any of identified genes. In conclusion our study revealed genetic alterations that were not previously associated with glioma pathogenesis and could be potentially used as molecular markers of different glioblastoma subtypes.

Association of CCND1 overexpression with KRAS and PTEN alterations in specific subtypes of non-small cell lung carcinoma and its influence on patients’ outcome

“…The primer sequences were as follows: 5′-TTC TGC CTT TGA TGT TAC-3′ (sense) and 5′-AGG CTG AAT CAA TGT CTT-3′ (antisense) for CCND1, and 5′-CTC TTT TCT TTC CCG ATA GGT-3′ (sense) and 5′-CTG GGA TGC TCT TCG ACC TC-3′ (antisense) for the ACTB. Genomic DNA (100 ng) was amplified with a pair of primers specific for each gene in the following ratio ACTB:CCND1=1:8 [18,19]. The PCR reactions were performed on the GeneAmp PCR System 9700 (Applied Biosystems, Foster City, CA, USA) under the following conditions: initial denaturation at 95°C for 10 min was followed by 30 cycles at 95°C for 1 min, at 55°C for 1 min, and at 72°C for 1 min, with final elongation at 72°C for 10 min.…”

Identification of potential novel biomarkers to differentiate malignant thyroid nodules with cytological indeterminate

“…It could activate protein C (APC) and inhibit blood coagulation [38]. The genetic mutation of this gene will result in autosomal dominant hereditary thrombophilia [39] and malignant glioma [40]. The PROS1 and FN1 others 12 genes alternations were identified as important diagnostic biomarkers for thyroid cancer through the meta-analysis the gene expression profiling of clinical thyroid nodules [41].…”

Caspase recruitment domain family member 10 regulates carbamoyl phosphate synthase 1 and promotes cancer growth in bladder cancer cells

“…Abnormal and ectopic CPS1 expression in tumour cells may lead to urea cycle deficiency and a nucleic acid pool imbalance . CPS1 overexpression is associated with poor prognosis in several types of cancer, such as colon cancer, cholangiocarcinoma and glioblastoma . CPS1 has also been reported to be regulated by hepatocyte nuclear factor 3β (HNF3β) and sirtuin 5 (SIRT5) by their transcriptional activation or deacetylation‐ and deglutarylation‐mediated activation .…”

“…15,16,29 CPS1 overexpression is associated with poor prognosis in several types of cancer, such as colon cancer, cholangiocarcinoma and glioblastoma. [30][31][32] CPS1 has also been reported to be regulated by hepatocyte nuclear factor 3β (HNF3β) and sirtuin 5 (SIRT5) by their transcriptional activation or deacetylation-and deglutarylation-mediated activation. [33][34][35] Thus, the results of our study might supplement the previous reported associations.…”