Mutation Analysis and Single Nucleotide Polymorphism of TP53 Gene in Breast Cancer in East Java

The Incidence of Indonesia breast cancer case in 2018 was reported at 20.7% or 160,653 in number. The factors that caused breast cancer is TP53 gene mutation and Single Nucleotide Polymorphism (SNP). This study aimed to determine the mutation and Single Nucleotide Polymorphism (SNP) of TP53 gene in breast cancer. Samples of this study were 9 people chosen based on a purposive technique. The methods include total DNA isolation, DNA quantification, PCR, and sequencing. The results of the sequencing were then analyzed using alignment and blast. The SNP is browsed by the SNP finder on NCBI both followed by protein modeling. The results of this study indicate the existence of mutation in the exon and intron regions. Substitution of Guanine (G) to base Adenine (A) is occur in codon 496 which is a coding region. SNP was also obtained in exon of sample 12. The conclusion of this study is breast cancer can be caused by mutations that occur in the exon and altered the structur of protein structure, so then affect the binding affinity between p53 and its target domain. Tp53 gene mutation is not the only cause of breast cancer staging development, there are other genes that also contribute to the development of cancer stage. In addition, Single Nucleotide Polymorphism in the TP53 gene can be used as a predisposition marker of breast cancer that has potential to be inherited

Clinicopathologic and Molecular Characteristics of Gastrointestinal MiNENs

BackgroundA mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN) is a recently defined entity that comprises a neuroendocrine tumor (NEN) component and a non-neuroendocrine tumor (nNEN) component. As MiNEN is a recently defined entity, its molecular nature is not well known. Here, we evaluated the clinicopathologic and molecular characteristics of gastrointestinal (GI) MiNENs.MethodsWe performed a genomic analysis of 31 samples from 12 GI MiNEN cases using next-generation sequencing. We examined the primary NEN and nNEN components, as well as the metastatic NENs and nNENs. The relationships between the clinical tumor features (component, location, and grade) and their molecular characteristics were examined.ResultsThe 12 MiNENs included in the study were found in the stomach (n=10), distal rectum (n=1), and anus (n=1). Primary MiNENs that had NENs as the major component showed a worse clinical outcome than those that had nNENs as the major component. All distant metastatic tumors originating from MiNENs were NENs. In addition, NENs generally carried 1.5 times more gene mutations and copy number variations than nNENs. The ATRX gene deletion and TP53 gene mutation were the most common variants in both components of GI MiNENs.ConclusionsWe have revealed the detailed clinicopathologic and molecular findings with distinguishable alterations of GI MiNENs. To our knowledge, this is the first study to report the ATRX gene deletion in GI MiNENs. The molecular characteristics of GI MiNENs could provide clues to the pathogenic origin and progression of GI MiNENs.

Prognostic Genomic Biomarkers for Acute Myeloid Leukemia (AML) Based on French-American-British (FAB) Subtypes

Background: The FAB classification system divides AML into eight subtypes, M0-M7, based on the blast cell morphology and its degree of myeloid maturation. It's an older system to classify AML, but is still used in some treatment protocols. Some prognostic factors related to patient and tumor characteristics have been previously described for AML, including age, Karnofsky score, and karyotype etc. However, the prognostic genomic biomarkers for detailed FAB subtypes of AML are not well defined. Design: Whole genome sequencing data were analyzed in 197 cases of AML. Twenty-four mutation genes and 38 copy number altered genes were selected based on change rate >=2% as a cutoff. Kaplan Meier Survival analysis for these genes was performed in five FAB subtypes (M0-M5). M6 and M7 are excluded from this study because of small sample size (M6, n=3; M7, n=3). All sequencing data and corresponding pathology information were from The Cancer Genome Atlas (Acute Myeloid Leukemia, TCGA provisional) and were analyzed via cBioPortal bioinformatics tool. Result: Total of seven mutation genes and two copy number altered genes show prognostic values. TP53 gene mutation is associated with worse overall survival in M0 (n=18). DNMT3A gene mutation is associated with worse overall survival in M1 (n=44). Gene mutations of NPM1, FLT3, IDH1 and gene amplification of KMT2A are associated with worse overall survival in M2 (n=44). BRINP3 gene mutation is associated with worse overall survival in M3 (n=21). TP53 gene mutation and gene amplification of KMT2A and ERG are associated with worse overall survival in M4 (n=39). KRAS mutation is associated with worse overall survival in M5 (n=22). (Log-rank test, p<0.05 for all tests) Conclusion: These data suggest that different FAB subtypes of AML could have unique prognostic genomic biomarkers. Compared with whole exome sequencing, targeted gene sequencing for these biomarkers may save time and money for patients. Further studies are necessary to understand the biological effects of these gene mutations/amplifications and confirm the above associations. Disclosures No relevant conflicts of interest to declare.