Association between CACNG2 polymorphisms (rs4820242, rs2284015 and rs2284017) and chronic peripheral neuropathic pain risk in a Mexican population.

OBJECTIVE: In animal models and humans, mutations in voltage-dependent calcium channel gamma-2 subunit gene (CACNG2) have been associated with neuronal hyperexcitability, including neuropathic pain. The objective of this study was to determine the allelic and genotypic frequencies of CACNG2 polymorphisms (rs4820242, rs2284015 and rs2284017) and their association with the risk of chronic peripheral neuropathic pain (CPNP) in the Mexican population. PATIENTS AND METHODS: Single nucleotide polymorphisms (SNPs) were determined by real-time PCR, and allelic and genotypic frequencies were compared between healthy Mexican subjects and CPNP patients. The risk of association of CACNG2 SNPs with the presence of CPNP and its characteristics was evaluated. RESULTS: The allele G (OR 2.08, p = 0.01) of rs2284015 was observed as a risk factor for developing CPNP. The allele A of rs4820442 showed a risk of association with a history of surgery (OR 3.92, p = 0.04), radiculopathy (OR 4.29, p = 0.0001), bilateral presentation of pain (OR 3.15, p = 0.003), and neuropraxia (OR 0.36, p = 0.01). The allele C of rs2284015 was associated with an increased risk of burning and allodynia. In the analysis of the association of genotype frequencies and inheritance patterns, as well as in the analysis of interaction with sex, a modification of risk was observed. CONCLUSIONS: The allele G of rs2284015 and the AGC haplotype of CACNG2 rs4820242, rs2284015 and rs2284017, regardless of sex and etiology could contribute to the risk of CPNP. Certain alleles and genotypes could constitute severity markers in CPNP with sex-biased effects; however, further studies are required to confirm these observations.

BECN1 protein expression is associated with poor survival in triple negative locally advanced breast cancer.

OBJECTIVE: The role that Beclin 1 (BECN1) plays in the development and progression of cancer mediated by autophagy, as well as its differential expression in breast cancer cell lines and mammary tumor tissue according to the molecular subtype, has been demonstrated. The objective of this study was to evaluate the association of BECN1 cytoplasmic expression with clinical and pathologic response, recurrence, disease-free survival (DFS) and overall survival (OS) in patients with locally advanced breast cancer (LABC), according to immunophenotype. PATIENTS AND METHODS: 64 patients with non-triple negative LABC and 20 patients with triple negative LABC who received preoperative chemotherapy were included in an observational, analytical and retrospective study to evaluate the cytoplasmic expression of BECN1 protein by immunohistochemistry in microarrays of breast cancer tissue obtained before treatment. Association between BECN1 and clinicopathological characteristics, clinical and pathologic response to preoperative chemotherapy and recurrence, were analyzed using Chi-square or Fisher's exact test. Postoperative DFS and OS were assessed by Kaplan-Meir curves, and the difference according to BECN1 expression was evaluated using the log-rank test. The bivariate analysis was performed using the Cox Proportional Hazards Model. A p-value of < 0.05 was considered statistically significant. RESULTS: BECN1 staining revealed positive expression in 62.5% of patients with non-triple negative and 60.0% with triple negative LABC. No association was observed between BECN1 expression and clinical or pathological response or recurrence. An association of the BECN1 expression with lower OS in triple negative breast cancer was found (HR = 5.19; 95% CI 1.12-24.02; p = 0.035). CONCLUSIONS: Results showed an association of the cytoplasmic expression of BECN1 with a lower OS, which could be a poor prognostic biomarker in triple negative LABC.

Characterization of NF1 frameshift mutations in pediatric patients with neurofibromatosis type I.

Neurofibromatosis type I is an autosomal dominant disease with complete penetrance and variable age-dependent expressivity. It is caused by heterozygous mutations in neurofibromin 1 (NF1). These occur throughout the length of the gene, with no apparent hotspots. Even though some mutations have been found repeatedly, most have been observed only once. This, along with the variable expressivity, has made it difficult to establish genotype-phenotype correlations. Here, we report the clinical and molecular characteristics of four pediatric patients with neurofibromatosis type I. Patients were clinically examined and DNA was extracted from peripheral blood. The whole coding sequence of NF1, plus flanking intronic regions, was examined by Sanger sequencing, and four frameshift mutations were identified. The mutation c.3810_3820delCATGCAGACTC was observed in a familial case. This mutation occurred within a sequence comprising two 8-bp direct repeats (GCAGACTC) separated by a CAT trinucleotide, with the deletion leading to the loss of the trinucleotide and the 8-bp repeat following it. The deletion might have occurred due to misalignment of the direct repeats during cell division. In the mutation c.5194delG, the deleted G is nested between two separate mononucleotide tracts (AAAGTTT), which could have played a role in creating the deletion. The other two mutations reported here are c.4076_4077insG, and c.3193_3194insA. All four mutations create premature stop codons. In three mutations, the consequence is predicted to be loss of the GAP-related, Sec14 homology, and pleckstrin homology-like domains; while in the fourth, only the latter two domains would be lost.

BIK/NBK gene as potential marker of prognostic and therapeutic target in breast cancer patients

PURPOSE: The purpose of this study is to determine the association between the BIK/NBK gene expression and estrogen receptor alpha expression. MATERIALS AND METHODS: We determined the association of BIK/NBK gene expression by real time quantitative reverse transcription polymerase chain reaction and estrogen receptor alpha expression by immunohistochemistry in samples of breast cancer tissue. RESULTS: We found a statistically significant correlation of BIK/NBK gene expression with the estrogen receptor alpha expression (ρ = 0.751, p = 0.004). For verify differences of BIK/NBK gene expression among ERα+ and ERα- breast cancer tissues, Mann-Whitney U test was performed, obtaining significant differences. CONCLUSIONS: BIK/NBK gene expression may have important clinical implications and provide predictive, prognostic or therapeutic marker in breast cancer patients according to the estrogen receptor alpha expression (AU)