Molecular evaluation of mutations in acute myeloid leukemia patients from Turkey: A single-center study.

ABSTRACT: Certain genetic mutations could have a role in the etiology of acute myeloid leukemia (AML). Hereby, in this study, we primarily aimed to investigate the distribution of genetic mutations in AML patients. We also attempted to analyze the incidence of genetic mutations in AML patients from Turkey.This retrospective study included a total of 126 patients diagnosed with AML, who had molecular mutation test results or records in their patient files. The patients who were not citizens of the Republic of Turkey were not included in the study.It was observed that analyses for at least 1 c-kit exon mutation had been carried out on 76 patients, which detected no c-kit mutation among the types of genetic mutations investigated in all of those 76 patients. We found the frequency of FMS-like tyrosine kinase 3-internal tandem duplication mutation as 25%. The prevalence of translocation(15;17) was approximately 11% and the prevalence of translocation(8;21) was % 6.25. In addition, we also showed that the frequency of inversion16 was nearly 3.7%.Lastly, the possibility of c-kit mutation in AML patients from Turkey might actually be low.

Investigation of Hereditary Cancer Predisposition Genes of Patients with Colorectal Cancer: Single-centre Experience.

OBJECTIVE: To investigate the genetic causes of colorectal cancers (CRCs); and to determine the genotype-phenotype correlation. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Medical Genetics, Diskapi Yildirim Beyazit Training and Research, Hospital, Ankara, Turkey, between January 2018 and January 2020. METHODOLOGY: 59 cancer susceptibility genes of 41 patients, included in the study and diagnosed with CRC, were examined using next generation sequencing (NGS) technique. Statistical analysis of the possible relationships among the mutation carrier status of the patients and the parameters of gender, age at diagnosis, and family cancer history, were performed. RESULTS: The mean age at diagnosis of all CRC patients was 48.7 years (range 28-74). Mutations in MLH1, MSH6, CHEK2, PMS2 and MUTYH genes were detected in 10 patients (24.4%). The mean age at diagnosis of CRC was 46.2 years in those who carried the mutation, while it was 49.5 years in those without. Carriers and non-mutation carriers, when compared in terms of age at diagnosis, gender, family cancer history, no significant difference was observed. CONCLUSION: Genes that may cause susceptibility to cancer may play a role in the etiopathogenesis of the CRC. NGS-based multigene panels allow these genes to be detected in the patient and to identify an inherited cancer syndrome. Key Words: Colorectal cancer, Lynch syndrome, Hereditary cancer, Gene, Next generation sequencing.

The Relationship of Mutation Carriage of BRCA1/2 and Family History in Triple-Negative Breast Cancer: Experience from a Diagnostic Center in Turkey.

OBJECTIVE: BRCA1/2 genes play a role in the etiopathogenesis of 10%-30% of triple-negative breast cancer (TNBC). This study aims to investigate the BRCA1/2 genes and the demographic and clinicopathological features in patients with TNBC. The study also examined the impact of cancer history of TNBC individuals' relatives on the risk of BRCA1/2 mutation carriership rate. MATERIALS AND METHODS: The BRCA1/2 genes of 65 women diagnosed with TNBC between 2011 and 2017 were investigated using next-generation sequencing. We analyzed the correlations of patients' demographic and clinicopathologic parameters and family history with BRCA1/2 mutation status. We used the χ2-test, t-test, Mann-Whitney U test, and logistic regression statistical methods. RESULTS: The BRCA1/2 mutation carrier rate was 16.9%. Patients who had BRCA1/2 mutations were compared with those who did not in terms of demographic and clinicopathological parameters. In the BRCA1/2 mutation carrier group, the Ki-67 index and the number of relatives with cancer were higher than the BRCA1/2 non-carrier group. Logistic regression analysis revealed that when the number of relatives with breast or ovarian cancer was ≥2, the risk of carrying the BRCA1/2 mutation increased by 15-fold. Regardless of the type of cancer (including cancers in other organs besides breast or ovary), the risk of carrying the BRCA1/2 mutation increased 1.3 times with each increase in the number of relatives with cancer for the patient with TNBC. CONCLUSION: In cases with a diagnosis of TNBC, a significant relationship exists between the number of relatives with cancer in the family history and the risk of carrying mutations in the BRCA1/2 genes. This relationship can be confirmed further by large-scale studies with more cases.

Novel BRCA2 pathogenic genotype and breast cancer phenotype discordance in monozygotic triplets.

BRCA1/2 genes with high-penetrance are tumor suppressor and tumor susceptibility genes that play important roles in the homologous recombination mechanism in DNA repair and increase breast cancer risk. Variants in BRCA1 or BRCA2 are the main causes of familial and early-onset breast cancer. This study investigated pathogenic variant belonging to the BRCA2 gene splice region in monozygotic triplets. A 44-year-old woman was diagnosed with breast cancer when she was 32 years old. Her monozygotic sister had a history of breast cancer. No malignancy was detected in the third one of the monozygotic triplets. Sanger sequencing was used to evaluate the BRCA1/2 gene status of the patient and family members. It was figured out that they had the same genetic variant, a heterozygous germ-line splice region variant (c.7008-1G > C) in the BRCA2 gene. This novel splice region variant may be a new pathogenic variant of the BRCA2 gene. Its association with breast cancers needs to be further verified in more patient cases.