Evaluation of BRCA1/2 Gene Mutations in Patients With High-Risk Breast and/or Ovarian Cancer in Turkey

Objectives To find BRCA1/2 test selection criteria unique to the Turkish population, as well as to provide the BRCA1/2 gene mutation distributions of patient population to the literature. Methods Genetic counseling was given to 2,373 cases with a family history of high-risk breast and/or ovarian cancer who applied to Istanbul University, Oncology Institute, Department of Cancer Genetics between 1994 and 2021 and selected by NCCN Guidelines for the BRCA1/2 test criteria. In our clinic, mutation screenings in BRCA1/2 genes were performed by Sanger sequencing method in patients admitted between 1994 and 2014 and by NGS method in patients admitted between 2015 and 2021. Results The overall mutation rate in our patient group selected from high-risk patients was 16.5% (391/2,373) after BRCA1/2 gene mutation screening performed in 2,373 cases who applied to the Cancer Genetics clinic. Of the patients with mutations, 57.5% (225/391) had BRCA1 mutation, 41.9% (164/391) had BRCA2 mutation, and 0.6% (2/391) had both BRCA1 and BRCA2 pathogenic mutations. People diagnosed before the age of 60 who have a history of triple-negative breast cancer had a 28.5% overall mutation rate. Conclusions BRCA1/2 mutation in Turkish population were evaluated in accordance with NCCN BRCA1/2 genetic test selection criteria; we discovered that all of our study results were statistically significant (p<0.05)

High Expression Level of miR-1260 Family in the Peripheral Blood of Patients with Ovarian Carcinoma

The most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America (USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous) monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future

OVER KANSERLERİNDE MİR-1260 MİKRORNA AİLESİNİN ARAŞTIRILMASI

Amaç: TÜİK-Türkiye istatistiklerine göre, Türkiye'de her yıl yaklaşık 2790 kişi over kanseri teşhisialmaktadır. Over kanseri hastalarının etkili bir şekilde tedavi edilebilmesi, tedavi sürecini takip edebilmesive erken aşamada tanı alabilmesi için hastalığa özgü ve hassas biyo-belirteçlere ihtiyaç vardır. Planlanan buçalışmada, miR-1260a ve miR-1260b moleküllerinin sporadik ve ailesel over kanseri vakalarının, sağlıklıkontrollerle karşılaştırılması sonucu invazif olmayan biyobelirteçler olup olmadığını belirlemeyiamaçlamaktadır.Gereç-Yöntem: Ailesel ve Sporadik Over kanseri olan 150 hasta ve bunlarla yaş, cinsiyet, etnik köken açıdaneşleştirilmiş 100 sağlıklı kontrollerle, miR-1260a ve miR-1260b ekspresyon düzeyleri karşılaştırıldı.Bulgular: Over kanseri hastalar ile sağlıklı kontrol grubu arasında her iki miRNA' nın da ekspresyonseviyeleri açısından istatistiksel olarak anlamlı bir fark olduğu (p = 0.000) görülmüştür. Sağlıklı kontrolleregöre, over kanserli hastalarda miR-1260a ve miR-1260b ekspresyonunun 16.1-43.21 kat aralığında arttığıbulundu. Bu moleküllerin diğer genlerle olan etkileşimlerini anlamak için STRING analizi yapıldı. Bu analizsonucunda; miR-1260a’nın hücresel translasyon aşaması üzerinde etkili olduğu bilinen ribozomal proteinailesi ile ilişkisi olduğu ve miR-1260b'nin, CHEK2 ve CDK4 proteinleri ile ilişkili olduğu bulundu.Sonuç: Öncelikle miR-1260a ve miR-1260b'nin anlamlı ekspresyon farkı over kanserli hastalar ile sağlıklıkontrollerin periferik kan lenfositleri arasında bulunmuştur. miR-1260a ve miR-1260b molekülleri, overkanseri etiyolojisinden sorumlu olabilir. miR-1260a ve miR-1260b moleküllerinin, over kanseri tanı veprognozunda invazif olmayan biyobelirteçler olarak kullanılabileceği düşünülmektedir

Aberrant miR-3135b and miR-1273g-3p expression in the peripheral blood samples of BRCA1/2 (±) ovarian cancer patients

Ovarian cancer (OC) ranks as the eighth most prevalent malignancy among women globally. The short non-coding RNA molecules, microRNAs (miRNAs) target multiple mRNAs and regulate the gene expression. Here in this study, we aimed to validate miR-3135b and miR-1273g-3p as novel biomarkers for prognostic and diagnostic factor OC. After RNA isolation, we analyzed the miR-3135b and miR-1273g-3p expression in peripheral blood samples derived from 150 OC patients. Subsequently, we compared their expression levels with 100 healthy controls. The differences of miR-3135b and miR-1273g-3p expression were detected using the Quantitative Real Time-PCR (qRT-PCR) technique following miRNA-specific cDNA synthesis pursing miRNA separation. The miR-3135b and miR-1273g-3p were higher in OC patients who tested positive for BRCA1/2 compared to BRCA-negative patients, and healthy cases. The level of miR-3135b demonstrated a roughly 4.82-fold increase in OC patients in comparison to the healthy cases, while miR-1273g-3p expression exhibited a roughly 6.77-fold increase. The receiver operating characteristic (ROC) analysis has demonstrated the potential of miR-3135b and miR-1273g-3p as markers for distinguishing between OC patients and healthy controls. The higher expressions of miR-3135b and miR-1273g-3p could be associated with OC development. Moreover, miR-3135b may have a diagnostic potential and miR-1273g-3p may have both diagnostic and prognostic potential in OC cell differentiation. The string analysis has revealed an association between miR-1273g-3p and the MDM2 gene, suggesting a potential link to tumor formation through the proteasomal degradation of the TP53 tumor suppressor gene. Additionally, the analysis indicates an association of miR-1273g-3p with CHEK1, a gene involved in checkpoint-mediated cell cycle arrest. String analysis also indicates that miR-3135b is associated with the MAPK1 gene, causing activation of the oncogenesis cascade. In conclusion, miR-1273g-3p, and miR-3135b exhibit significant potential as diagnostic markers. However, further research is needed to comprehensively investigate these miRNAs diagnostic and predictive characteristics in a larger cohort

OVER KANSERLİ HASTALARDA MİR-16-5P, MİR-17-5P VE MİR-638 EKSPRESYON DÜZEYLERİNİN ARAŞTIRILMASI

Amaç: Over kanseri, kadınlar arasında en ölümcül jinekolojik malignitelerden biridir. Birçok miRNA'nınonkogenler, tümör baskılayıcılar ve hatta kanser kök hücreleri ve metastazı modülatörleri olarak etki ettiğibelirlenmiştir. Daha önce yapılan mikroarray çalışmasından elde edilen bulgulara dayanarak, miR-16-5p,miR-17-5p, miR-638'in over kanseri etiyolojisinde önemli olabileceği düşünülerek, daha geniş populasyonluhasta ile sağlıklı kontrol grubu içerisinde araştırıldı. Bu çalışmanın amacı, üç riskli miR-16-5p, miR-17-5p,miR-638 molekülünün, yüksek riskli over kanseri olan hastaların erken tanısında ve prognozunda herhangibir biyobelirteç olup olmadığını doğrulamak ve tespit etmektir.Gereç-Yöntem: Çalışmada, over kanserli 142 hastanın periferik kan örnekleri ile etnik köken, yaş ve cinsiyetbakımından hasta populasyonu ile eşleştirilmiş 97 sağlıklı kontrol grubu kullanıldı. Gen ekspresyon analizleriiçin Real-Time PCR yöntemi uygulandı.Bulgular: miRNA gen ekspresyon düzeyleri, hasta gruplarında sağlıklı kontrollere kıyasla 2 kattan fazla arttıve istatistiksel olarak anlamlıydı (p &lt;0.05). Her miRNA için elde edilen p değeri, miR-16-5p, p &lt;0.001; miR-17-5p, p &lt;0.001, miR-638, p = 0.005 olarak bulundu. Ek olarak, miRNA'lı hastaların klinik verilerinikarşılaştırdığımızda; hastaların sigara içme durumu ile artmış miR-17-5p ekspresyon düzeyi arasındaanlamlı bir fark vardı (p = 0,007). Ayrıca, miR-638 uzak metastaz-pozitif hastalarda, uzak metastaz-negatifhastalardan anlamlı derecede daha yüksek düzeylerde eksprese edildi (p = 0.03).Sonuç: Bulgular, bu miRNA'ların metastaz ile ilişkili olduğunu göstermektedir. miR-16-5p, miR-17-5p vemiR-638 over kanserini tespit etmek ve ilerlemesini göstermek için potansiyel biyobelirteçler olabilir

FGFR4 c.1162G > A (p.Gly388Arg) Polymorphism Analysis in Turkish Patients with Retinoblastoma

Purpose. Various molecular variations are known to result in different gene variants in the FGFR4 gene, known for its oncogenic transformation activity. The goal of this study was to investigate the FGFR4 p.Gly388Arg variant that plays role in the progression of cancer and retinal growth and may be an effective candidate variant in the Turkish population in retinoblastoma patients with no RB1 gene mutation. Methods. Using the Sanger sequencing methods, the FGFR4 p.Gly388Arg variant was bidirectionally sequenced in 49 patients with non-RB1 gene mutation in retinoblastoma patients and 13 healthy first-degree relatives and 146 individuals matched by sex and age in the control group. Results. In Turkish population-specific study, the FGFR4 p.Gly388Arg variant was found in 27 (55.1 percent) of 49 patients; mutation was found in 7 (53.8 percent) of these patients’ 13 healthy relatives screened. When FGFR4 p.Gly388Arg mutation status is evaluated in terms of 146 healthy controls, in 70 (47.9 percent) individuals, mutation was observed. Our analysis showed that the FGFR4 p.Gly388Arg allele frequency, which according to different databases is seen as 30 percent in the general population, is 50 percent common in the Turkish population. Conclusions. In patients with advanced retinoblastoma who were diagnosed with retinoblastoma prior to 24 months, the FGFR4 p.Gly388Arg allele was found to be significantly higher. As a result, these results indicate that the polymorphism of FGFR4 p.Gly388Arg may play a role in both the development of tumors and the progression of aggressive tumors