Mutational profile of hereditary breast and ovarian cancer - Establishing genetic testing guidelines in a developing country.

Purpose: Because many countries lack the capacity to follow the international guidelines for genetic testing, we suggest the specific approach for establishing local genetic testing guidelines that could be applied in developing countries. We focus on hereditary breast (BC) and ovarian cancer (OC) in Serbia.

Methods: From the cohort of 550 persons who were referred for genetic counseling at the Institute for Oncology and Radiology of Serbia, 392 were selected.

Expression of SIRT1, SIRT3 and SIRT6 Genes for Predicting Survival in Triple-Negative and Hormone Receptor-Positive Subtypes of Breast Cancer.

Triple-negative breast cancer (TNBC) is characterized by aggressive phenotype and a poorer prognosis compared to the estrogen and progesterone receptor positive, Her2 negative (ER + PR + Her2-) breast cancer. Increasing evidence suggests that sirtuins, a family of histone deacetylases, could have an important role in aggressiveness of TNBC's. The current study evaluated the potential clinical relevance of SIRT1, SIRT3 and SIRT6 gene expressions in two prognostically distinctive subtypes of breast cancer, the most aggressive TNBC and the least aggressive ER + PR + Her2- tumors.

Confirmation of damaging effect of MSH2 c.2634+1G>C mutation on splicing, its classification and implications for counseling.

Introduction: Lynch syndrome (LS) is predisposing mainly to colorectal and endometrial carcinomas, but also to urinary tract cancers. LS association with upper urinary tract carcinomas is known, but its association with bladder cancer is not so clear. Confirmation of pathogenicity of detected mutations in LS-associated genes is required for adequate counseling.

Germline mutations in cancer susceptibility genes in high grade serous ovarian cancer in Serbia.

Clinical criteria for genetic testing of genes other than BRCA1/2 in epithelial ovarian cancer (EOC) still do not exist. We assessed the frequency and predictors of deleterious mutations in 19 cancer predisposition genes in high-grade serous ovarian cancer (HGSOC) in Serbia. Next-generation sequencing was used to identify germline mutations in the whole coding regions of a gene panel.

Association of uPA and PAI-1 tumor levels and 4G/5G variants of PAI-1 gene with disease outcome in luminal HER2-negative node-negative breast cancer patients treated with adjuvant endocrine therapy.

Background: The aim of this study was to evaluate the prognostic potential of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) tumor tissue levels and examine the association between these biomarkers and classical prognostic factors in early node-negative luminal breast cancer patients. The clinical value of 4G/5G variants of PAI-1 gene was evaluated.

Patients And Methods: This study involved 81 node-negative, estrogen receptor-positive and/or progesterone receptor-positive and human epidermal growth factor receptor 2-negative operable breast cancer patients who underwent radical surgical resection and received adjuvant endocrine therapy.

Promoter hypermethylation of p16, BRCA1 and RASSF1A genes in triple-negative breast cancer patients from Serbia.

Purpose: In order to investigate if aberrant promoter methylation of p16, BRCA1 and RASSF1A genes contributes to biological behavior of triple-negative breast cancer (TNBC), marked as the most aggressive phenotype of breast cancer, we compared the hypermethylation pattern between TNBC and ER+PR+Her2- breast cancer.

Methods: 131 patients with histologically confirmed breast cancers were included - 61 TNBC and 70 ER+PR+Her2- cases. The patients were followed up for 1-87 months (median 78).

Novel BRCA1 splice-site mutation in ovarian cancer patients of Slavic origin.

Mutations in breast cancer susceptibility gene 1 (BRCA1) lead to defects in a number of cellular pathways including DNA damage repair and transcriptional regulation, resulting in the elevated genome instability and predisposing to breast and ovarian cancers. We report a novel mutation LRG_292t1:c.4356delA,p.

Polymorphisms in cancer susceptibility genes XRCC1, RAD51 and TP53 and the risk of breast cancer in Serbian women.

Background: Thanks to immense improvements in technology over the past few decades, we have witnessed a major shift towards the idea that breast cancer results from a combined effect of multiple common alleles conferring low risk. This study investigates the role of 3 nonsynonymous SNPs in the DNA repair genes XRCC1 (R399Q), RAD51 (G135C) and TP53 (Arg72Pro) in breast cancer in Serbian women.

Patients And Methods: Cases of BRCA1/2-negative hereditary breast cancer (n = 52), sporadic breast cancer (n = 106) and age-matched cancer-free female controls (n = 104) were obtained from the Institute for Oncology and Radiology of Serbia's blood bank.

RAD51C mutation screening in high-risk patients from Serbian hereditary breast/ovarian cancer families.

Background: In 2010 an important finding was published showing that heterozygous mutations in RAD51C were highly penetrant and were able to confer an increased risk for breast and ovarian cancers. The role of possible third high penetrance breast cancer susceptibility gene was assigned to RAD51C.

Objective: Because of its rising importance in breast cancer development and the lack of information about RAD51C in Slavic populations, our goal was to identify potential population specific mutations in this gene in order to determine more detailed genetic screening strategy and breast cancer risk assessment.

RAD51 135G>C and TP53 Arg72Pro polymorphisms and susceptibility to breast cancer in Serbian women.

Breast cancer is a complex disease with both genetic and environmental factors involved in its etiology. An important role of polymorphisms in genes involved in DNA repair has been reported related to breast cancer risk. We conducted a case-control study in order to investigate the association of RAD51 135G>C and TP53 Arg72Pro polymorphisms with breast cancer in Serbian women.

Serbian high-risk families: extensive results on BRCA mutation spectra and frequency.

Mutations in BRCA genes elevate risk for breast and ovarian cancer. These mutations are population specific. As there are no data on BRCA mutation screening on larger number of probands in Serbia to date, aim of this study was to determine types and frequencies of BRCA mutations in individuals from high-risk families from Serbia, as well as to determine which BRCA mutations may be considered as founder for Serbian population.

Combined NGS approaches identify mutations in the intraflagellar transport gene IFT140 in skeletal ciliopathies with early progressive kidney Disease.

Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib-polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer-Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development.

Screening of the DNA mismatch repair genes MLH1, MSH2 and MSH6 in a Greek cohort of Lynch syndrome suspected families.

Background: Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure.

Novel BRCA1/2 mutations in Serbian breast and breast-ovarian cancer patients with hereditary predisposition.

Mutations in breast cancer susceptibility (BRCA) genes lead to defects in DNA repair processes resulting in elevated genome instability and predisposing to breast and ovarian cancer. The study was designed to detect mutational spectra of BRCA1/2 genes in a Serbian population. Using automated DNA sequencing, we tested individuals for BRCA mutations, based on positive family history of either breast or ovarian cancer or both.

Gene hypermethylation in tumor tissue of advanced oral squamous cell carcinoma patients.

Oral squamous cell carcinoma (OSCC) is characterized by high mortality rate and rising incidence. The aim of this study was to examine the methylation of particular tumor suppressor genes promoters in OSCC and to correlate the methylation status with the tumor-host features and patients survival. The genes selected for our investigation are involved in key cellular processes of malignant transformation, including cell cycle control (p16), apoptosis (Death Associated Protein Kinase, DAPK), Wnt signaling (Adenomatous Polyposis Coli, APC), cell-cell adhesion (E-cadherin, E-cad), and DNA repair (O(6)-methylguanine-DNA methyltransferase, MGMT, Werner syndrome gene, WRN).

cDNA microarrays: identification of gene signatures and their application in clinical practice.

Sequencing of human genome introduced the new postgenomic era in medicine. A novel microarray technology represents a novel genetic platform which is being widely exploited to bridge the gap between gene sequence and function. Basically, with this technique it is possible to simultaneously measure the activity of virtually all genes in the genome.

p53 mutations and human papillomavirus infection in oral squamous cell carcinomas: correlation with overall survival.

Purpose: The study investigated the pattern of p53 gene mutations and human papillomavirus (HPV) infection concerning their relation to overall survival in patients with oral squamous cell carcinomas of the tongue and floor of the mouth.

Patients And Methods: The presence of HPV infection in 50 patients, and p53 gene mutations (42 patients from the same group) in the tumour specimens were analysed by polymerase chain reaction and single-stranded conformational polymorphism method. The follow-up period ranged from 12 to 48 (median 29) months.

[Recommendations for treatment of individuals at risk for hereditary breast and ovarian carcinoma].

Germline mutations in BRCA 1 and BRCA 2 gene have been recognized as hereditary predisposition for breast and ovarian cancer for many years. The optimal clinical management of individuals at risk for hereditary breast and ovarian cancer are not completely defined. Current surveillance options are restricted in their effectiveness as well as limitations of the techniques.