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S-adenosylhomocysteine hydrolase deficiency is an autosomal recessive neurometabolic disorder affecting the muscles, liver, and nervous system. The disease occurs by pathogenic variants of AHCY gene encoding S-adenosylhomocysteine hydrolase (AHCY) enzyme. This article reports a patient with presumed AHCY deficiency who was diagnosed by whole exome sequencing due to compound heterozygosity of novel p.T57I (c.170C>T) and p.V217M (c.649G>A) variants of AHCY gene. The patient had diffuse edema, coagulopathy, central nervous system abnormalities, and hypotonia. She died in 3 months due to cardiovascular collapse. Clinical findings of the present case were compatible with previously reported AHCY deficiency patients and the novel variants we found are considered to be the cause of the symptoms. This article also compiles the previous reports and expands clinical spectrum of AHCY deficiency by adding new features.

Bone marrow aspirate for morphology and cytogenetics and qualitative reverse transcriptase polimerase chain reaction on peripheral blood cells is mandatory for the diagnosis of chronic myeloid leukemia (CML). Bone marrow biopsy and fluorescence in situ hybridisation may be necessary in selected patients. Performing other tests and diagnostic procedures depends on characteristics of the individual patient. Although flow cytometry is an essential tool in the diagnosis and monitoring of many hematological malignancies, it has a limited role in CML. In this study, we evaluated the CD45 side scatter results of our CML patients at diagnosis and during follow up. Totally 56 CML patients (22 female and 34 male) in chronic phase treated with imatinib were included. Patients were also evaluated after 8 (3-19) months follow up. Complete blood cound parameters and CD45/SSC results of the patients at diagnosis and follow up were evaluated retrospectively. The Wilcoxon T test was used to compare the means between the two groups. p, Morfoloji ve sitogenetik için kemik iliği aspiratı ve periferik kan hücrelerinde kalitatif revers transkriptaz polimeraz zincir reaksiyonu, kronik miyeloid lösemi (KML) tanısı için zorunludur. Seçilmiş hastalarda kemik iliği biyopsisi ve floresan in situ hibridizasyon gerekli olabilir. Diğer testlerin ve teşhis prosedürlerinin uygulanması, bireysel hastanın özelliklerine bağlıdır. Akış sitometrisi birçok hematolojik malignitenin tanısında ve izlenmesinde önemli bir araç olmasına rağmen, KML'de sınırlı bir rolü vardır. Bu çalışmada KML hastalarımızın tanı anında ve takip sırasındaki CD45 dağılım sonuçlarını değerlendirdik. İmatinib ile tedavi edilen kronik fazdaki toplam 56 KML hastası (22 kadın ve 34 erkek) çalışmaya dahil edildi. Hastalar ortalama 8 (3-19) aylık takipliydi. Hastaların tanı ve takipteki tam kan sayımı parametreleri ile CD45/SSC sonuçları retrospektif olarak değerlendirildi. İki grup arasındaki ortalamaları karşılaştırmak için Wilcoxon T testi kullanıldı. p

Deletion 13q [del(13q)] is a favorable prognostic marker if it is detected as a sole abnormality in chronic lymphocytic leukemia (CLL). However the clinical courses of cases with isolated del(13q) are quite heterogeneous. In our study, we investigated copy number variations (CNVs), loss of heterozygosity (LOH), and the size of del(13q) in 30 CLL patients with isolated del(13q). We used CGH+SNP microarrays in order to understand the cause of this clinical heterogeneity. We detected del(13q) in 28/30 CLL cases. The size of the deletion varied from 0.34 to 28.81 Mb, and there was no clinical effect of the deletion size. We found new prognostic markers, especially the gain of 16p13.3. These markers have statistically significant associations with short time to first treatment and advanced disease stage. Detecting both CNVs and LOH at the same time is an advantageous feature of aCGH+SNP. However, it is very challenging for the array analysis to detect mosaic anomalies. Therefore, it is very important to confirm the results by FISH. In our study, we detected approximately 9% mosaic del(13q) by microarray. In addition, the gain of 16p13.3 may affect the disease prognosis in CLL. However, additional studies with more patients are needed to confirm these results.

Chronic lymphocytic leukemia (CLL) is known as type of leukemia originating from clonal mature B lymphocytes and has genetic heterogeneity. Many studies have been done to clarify the genome of CLL. In these studies, del(13q) is reported as the most common chromosomal aberration. Although this anomaly is associated with good prognosis when isolated, patients have clinical heterogeneity. In addition, in many gene mutations including TP53, NOTCH1 and SF3B1 gene mutations, poor prognosis has been identified. The prognostic significance of these genes has begun to be demonstrated. According to these data, we aimed to determine the mutation rate of NOTCH1 and SF3B1 genes and to investigate the prognostic effects (disease stages, TTFT and OS) in 43 cases with isolated del(13q) by using FISH method. We investigated the most common mutations of NOTCH1 and SF3B1 gene in CLL by using Sanger sequencing method. While frameshift 7541_7542delCT mutation was detected in the NOTCH1 gene in 1 out of 42 CLL cases with clinical heterogeneity, mutation in the SF3B1 gene couldn’t be detected. As a result of our study, it was observed that NOTCH1 and SF3B1 gene mutations weren’t associated with isolated del(13q) which is compatible with the literature data. Our study is the first study that evaluates NOTCH1 and SF3B1 gene mutations with prognostic parameters of isolated del(13q) with CLL patients in the Turkish population. As a result; It was concluded that there may be different reasons responsible for the clinical heterogeneity of isolated del(13q) cases and further studies are needed to reveal these reasons, Kronik lenfositik lösemi (KLL) klonal matür B lenfositten kaynaklanan ve genetik heterojenite gösteren bir lösemi tipi olarak bilinmektedir. KLL’nin genomunun aydınlatılması için birçok çalışma yapıldığı görülmektedir. Bu çalışmalarda, kromozomal aberasyonlardan en sık del(13q)’nun meydana geldiği bildirilmektedir. Bu anomali izole olduğu durumda iyi prognoz ile ilişkilendirilmesine rağmen, hastalar klinik heterojenite göstermektedir. Bunun yanında kötü prognoz ile ilişkilendirilen TP53, NOTCH1 ve SF3B1 gen mutasyonlarının da bulunduğu bir çok gende mutasyonlar tanımlanmış ve prognostik önemleri ortaya koyulmaya başlanmıştır. Biz de, bu veriler doğrultusunda FISH yöntemiyle izole del(13q) saptadığımız 43 olguda NOTCH1 ve SF3B1 genlerinin mutasyon oranını belirlemeyi ve prognoza (hastalık evreleri, TTFT ve OS) olan etkisini araştırmayı hedefledik. KLL’de en sık gözlenen NOTCH1 ve SF3B1 gen mutasyonlarını Sanger sekanslama yöntemi ile araştırdık. Klinik heterojeniteye sahip KLL olgu grubumuzun, 1/42’sinde NOTCH1 geninde frameshift 7541_7542delCT mutasyonu saptanırken, SF3B1 geninde mutasyon tespit edemedik. Çalışmamız sonucunda, NOTCH1 ve SF3B1 gen mutasyonlarının literatür verileri ile uyumlu olarak izole del(13q) ile ilişkili olmadığı gözlenmiştir. Çalışmamız Türk populasyonunda izole del(13q) KLL hastalarında prognostik parametreler ile birlikte NOTCH1 ve SF3B1 gen mutasyonlarının değerlendirildiği ilk çalışma olma özelliğindedir. Sonuç olarak; izole del(13q) vakalarının klinik heterojenitesinden sorumlu başka nedenlerin de olabileceği ve bunların ortaya çıkarılmasını amaçlayan daha fazla çalışmaya ihtiyaç olduğu sonucuna varılmıştır.

Melanositik nevus (MN) orneklerini histopatolojik olarak malign melanomdan (MM) ayirmak bazen zor olabillmektedir. Floresan in situ hibridizasyon (FISH)’in ciltteki melanositik neoplazmlarin teshisinde kullanildigi kanitlanmistir. Bu calismada standart melanom FISH testinin (RREB1, CCND1, MYB genlerini ve sentromer 6'yi hedefleyen 4 yollu prob) ve ayrica EGFR, TP53, MDM2 ve TP53 genlerini hedefleyen problarin melanomlari melanositik nevuslerden ayirmadaki etkinligi arastirilmistir. 24 MM ve 24 MN orneklerine standart FISH testi uygulandi. Ancak EGFR, TP53, MDM2 ve TP53 gen kopya sayilari FISH yontemi kullanilarak 24 MN ve 16/24 MM orneklerinde incelendi. Floresan in situ hibridizasyon ile saptanan pozitif genomik kopya aberasyonlarinin (4 yollu prob ve digerleri) gorulme sikligi 24 MM vakasinda %83,3 ve 24 MN'de %5,2 olarak belirlendi. Malign melanom ve MN gruplari arasinda CCND1, RREB1, EGFR amplifikasyonlari acisindan istatistiksel olarak anlamli farkliliklar bulundu (p 0,05). Ek olarak, 5 akral lentijinoz melanomun tumu analiz edilebildi ve hepsi EGFR amplifikasyonu acisindan pozitifti. Sonuc olarak, CCND1, RREB1 ve EGFR amplifikasyonlari MM icin tanisal oneme sahip oldugu ve FISH testinin, histopatolojik yontemlere ek olarak kullanilmasinin etkili olabilecegi sonucuna varilmistir. Ancak, yanlis pozitif sonuclardan kacinmak icin sentromer kontrollu problar kullanilmasi gerekliligi gozlenmistir.

Background: deletion of 13q14 [del(13q)] is the most common cytogenetic change (50%) in chronic lymphoblastic leukemia (CLL), and it is a good prognostic factor if it is detected as a sole aberration by FISH. However, it is observed the clinical course of CLL cases with del(13q) are quite heterogeneous and the responsible for this clinical heterogeneity has not been established yet. Some investigators suggest type II deletion (include RB1 gene) is associated with more aggressive clinical course. Also, it is suggested that the deletion burden and the deletion type have a prognostic effect. In this study, we aimed to investigate the effect of RB1 gene deletion, deletion burden and deletion type on overall survival (OS), disease stage and time to first treatment (TTFT) in patients with isolated del(3q). Sixty eight cases, detected isolated del(13q) were included in the study. Also, RB1 deletion was analyzed from peripheral blood of them using FISH. Results: RB1 deletion was detected in 41% of patients, but there was no statistically significant difference between RB1 deletion and TTFT, stage and OS (p > 0.05). At same time, statistically significant difference was detected between high del(13q) (> 80%) and TTFT (p < 0.05). Conclusion: the statistical analysis of our data regarding to the association between RB1 deletion and deletion type, TTFT, disease stage, and OS has not confirmed type II deletion or biallelic deletion cause poor prognosis. However, our data supports the deletion burden has a prognostic effect. More studies are needed to elucidate the cause of the clinical heterogeneity of CLL cases with del(13q)., Turkish Society of Hematology

In acute myeloid leukemia, t(8;21) detected with a frequency of 10% is associated with good prognosis. However, variant t(8;21) is observed in 4% of these cases, and although the prognostic effects of these variant translocations have not been clearly revealed, there are findings that they affect the prognosis poorly. Here, we report on a 39 years old man, detected 4-way varyant t(8;21) which include relocalization of RUNX1/RUNX1T1 fusion gene, and loss of Y chromosome. RT-PCR also confirmed RUNX1/RUNX1T1 fusion transcript. Additionally, D820G and N822K mutations on KIT gene and mut B on NMP1 gene were detected. A complete remission could not achieved after first chemotherapy treatment. Due to primary resistance and variant of t(8;21), stem cell transplantation was performed. The variant translocation we have reported is unique and also the case is the second case that was reported in the literature in terms of the relocation of the AML1/ETO fusion gene. Since c-KIT mutations and LOY were also observed, it is not possible to predict the prognosis. To highlight the importance of variant translocations and relocalization of fusion gene, more cytogenetic and molecular data are needed.

BACKGROUND: Promoter hypermethylation and global hypomethylation in the human genome are hallmarks of most cancers. OBJECTIVE: The aim of this study is to assess the methylation profile patterns of TWIST gene and to investigate the relationship of methylation with pathological features. METHODS: Romoter CpGisland methylation of TWIST which can be related in breast cancer was performed by methylation-sensitive high resolution melting (MS-HRM) analysis. Formalin-fixed, paraffin-embedded (FFPE) tissue samples of 80 patients with a diagnosis of primary breast cancer from Eskisehir Osmangazi University medical faculty of Oncology Clinic were included. RESULTS: In our study, the promoter hypermethylation frequency of TWIST gene was 25.0%. With these results, when the prognostic factors of the patients were analyzed, tumor stage and age were found to be meaningless with the hypermethylation of TWIST gene, but found to be significant with lymph node positivity, ER positivity, PR negativity, and HER2/NEU negativity. CONCLUSION: Our study is important as being the first study that analyzes association between histopathologic type and TWIST gene promotor methylation status in Turkish population.

FMF siklikla Akdeniz cevresinde yasayan etnik gruplari etkileyen, otozomal resesif gecisli bir hastaliktir. FMF’e yol acan MEFV geninin kodladigi Pirin proteinin antiinflamatuar yanitta negatif bir duzenleyici olarak rol oynadigi dusunulmektedir. FMF hastalarinin cogundan MEFV gen mutasyonlarinin sorumlu oldugu dusunulmektedir. Bu calismada, FMF tanisi almis 5836 olgunun MEFV genindeki olasi mutasyonlarinin tespit edilmesi ve tespit edilen mutasyonlarin Turk FMF olgulari arasindaki dagiliminin degerlendirilmesi amaclanmistir. FMF tanisi almis, 7 yillik hasta profili ile retrospektif bir calisma yapilmistir. Olgulardan elde edilen DNA orneklerinden, pirosekanslama ile MEFV geninde hastalikla iliskisi oldugu bilinen 22 mutasyon bolgesi calisilmistir. Toplam 5836 olgunun 2774’unde (% 47,5) mutasyon saptanirken, 3062’sinde (% 52,46) incelenen bolgelere iliskin mutasyon gozlenmemistir. .Calisma grubundaki 5836 olgunun % 18,59’de M694V, % 12,15’de E148Q, % 7,4’de V726A, % 3,56’de M680I (G>C), % 2,59’de M680I (G>A), %1,85’de R761H, % 1,9’de P369S ve %1,25’de K695R mutasyonlari tespit edilmistir. Bu calismada elde edilen bulgular dogrultusunda, Turk toplumundaki MEFV gen mutasyon tipleri ve frekanslari genis bir hasta serisiyle net bir sekilde ortaya konulmustur. Bu verilerin Turk toplumunda yeni FMF panelleri icin daha spesifik belirteclerin kullanilmasina yardimci olabilecegini dusunmekteyiz.

Background: Breast cancer is the most common cancer in women. Histopathology plays an important part in determining the treatment strategy for women with breast cancer. GSTP1 plays an important role in protecting cells from cytotoxic and carcinogenic agents and it is expressed in normal tissues at variable levels in different cell types. CDH1 plays a critical role for establishment and maintenance of polarity and differentiation of epithelium during the development period. Also, it plays an important role in signal transduction, differentiation, gene expression, cellmotility and inflammations. Methods: In this study the promoter methylation levels of GSTP1 and CDH1 gene which are associated with breast cancer were investigated by technique of Methylation Sensitive High Resolution Melting Analysis (MS-HRM). We analysed primary tumor core biopsies from 80 high-risk primary breast cancer patients (tumors ≥ 2 cm and/or lymphatic metastase and/or distant metastases and/or under 40 years). Also the patients’ histopathologic types were associated with the methylation levels. Results: In our study the promoter hypermethylation status was observed at different rates; GSTP1 and CDH1 hypermethylation frequencies were 82% and 95% respectively. The promoter hypermethylation levels of the genes were found to be significant with lymph node positivity, ER positivity and HER2/neu negativity. Conclusion: Our study is important as being the first study that analyzes association between histopathologic type and GSTP1 and CDH1 gene promotor methylation status in Turkish population.

Just as its clinical heterogeneity, genetic basis of Frontotemporal dementia (FTD) is also diverse and multiple molecular pathways are thought to be involved in disease pathogenesis. In the present study, FTD-related genes were evaluated in a Turkish cohort of 175 index FTD patients with a gene panel including GRN, MAPT, TARDBP, FUS, CHMP2B and VCP genes. Potential genetic associations were prospected in 16 patients (9.1%); five variants (p.(Gly35Glufs) and p.(Cys253Ter) in GRN; p.(Arg95Cys) in VCP; p.(Met405Val) in TARDBP and p.(Pro636Leu) in MAPT) were classified as pathogenic (P) or likely pathogenic (LP), in four familial and one sporadic patients. Three novel variants in MAPT, CHMP2B and FUS were also identified in familial cases. The most common pathogenic variants were observed in the GRN gene with a frequency of 1.14% (2/175) and this rate was 4.57% (8/175), including variants of uncertain significance (VUS). In this study with the largest cohort of Turkish FTD patients, GRN and MAPT variants were identified as the most common genetic associations; and rare causes like VCP, TARDBP, CHMP2B and FUS variants are recommended to be considered in patients with compatible clinical findings. (C) 2021 Elsevier Inc. All rights reserved.

OBJECTIVE Breast cancer (BC) is a heterogeneous malignancy and differs widely among different patients. The aim of this study was to investigate the relationship between the HER2/TOP2A gene aberrations and promoter methylation in RASSF1A/APC genes in patients with high-risk BC. METHODS Formalin-fixed paraffin embedded (FFPE) tissue samples from primary breast tumors (n=60) were assessed. HER2/TOP2A aberrations was evaluated using FISH method. DNA was extracted from FFPE tumor tissues, and Methylation-sensitive high resolution melting (MS-HRM) analysis were performed for RASSF1A/APC genes methylation status. RESULTS HER2 amplification and TOP2A aberration were observed in 15/60 (25%) and 18/60 (30%) cases, respectively. According to the statistical analysis, HER2 amplification was associated with higher tumor grade (p=0.001), PR status (p=0.025), and TOP2A aberrations (p=0.004). RASSF1A and APC methylation were 58/60 (96.6%) and 26/60 (43.3%), respectively. There was a significant correlation between APC methylation and TOP2A aberration. APC gene methylation was significantly more frequent in tumors with TOP2A aberration (p=0.026). CONCLUSION Our results suggested that APC gene promoter hypermethylation was associated with TOP2A gene aberrations in patients with high-risk BC. This may be significant for targeted individual therapy. Additionally, it was confirmed that there was significant association of TOP2A gene aberrations with the HER2 gene amplification seen in BC. WOS:000518098600002 2-s2.0-85080872329

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common form of the dementia which is characterized by the accumulation of amyloid plaques at the extracellular compartment and formation of neurofibriller tangles at the intracellular compartment which results in the degeneration of the neuron bodies and synapses. APOE gene polymorphisms in late-onset AD have a significant effect on cellular levels and also have been associated with neuropathological conditions. To determine the effect of APOE gene polymorphisms on Alzheimer's patients, we have included 629 AD patients between 45-90 years and 200 healthy subjects into the study. APOE gene isoforms were determined by real-time PCR method. APOE genotype distributions were significantly different between the patient and control groups (p

Frontotemporal lobar degeneration (FTLD) describes a group of progressive brain disorders. The expansion of a noncoding GGGGCC (G(4)C(2)) hexanucleotide repeat in the C9orf72 gene is a major cause of both familial FTLD and amyotrophic lateral sclerosis. The aim of this study was to determine the prevalence of C9orf72 G(4)C(2)-repeat expansion in a Turkish population with FTLD and to determine its effects on the phenotype. The G(4)C(2) expansion in the C9orf72 gene was analyzed in 100 cases of FTLD without mutations of the MAPT, PGRN, CHMP2B, VCP, TARDBP, and FUS genes and 100 age-matched healthy controls by using repeat-primed polymerase chain reaction and fragment length analysis techniques. A possible pathogenic repeat (>= 30) was found in one of the familial cases (1/33), but none of the sporadic cases. The difference in the allele length between the cases and controls was statistically significant (p < 0.01). Intermediate (20-30) repeats were detected in 4% of our cases. Patients with psychotic symptoms appear to be enriched for intermediate and possibly pathogenic repeats. To determine whether the intermediate and >= 30-repeat allele carriers shared the C9orf72 risk haplotype, we examined rs4879515 and rs3849942 in all samples and family members of patients with possibly pathogenic alleles. We identified at least one risk allele for each single-nucleotide polymorphism in all intermediate and possibly pathogenic repeat carriers. We observed that >= 8 unit repeats were strongly correlated with the tagging risk alleles for both single-nucleotide polymorphisms (p < 0.001). To our knowledge, this is the first study to evaluate C9orf72 G(4)C(2) repeats in Turkish patients with FTLD. The present findings suggest that pathogenic expansions of the C9orf72 repeat are uncommon in Turkish patients with FTLD, but intermediate repeats may be a risk factor for FTLD and act as a genetic modifying factor for psychotic symptoms. (C) 2018 Elsevier Inc. All rights reserved.

The purpose of this study was to determine the frequency of BCL2, BCL6, IGH, TP53, and MYC protein expression and rearrangements of the respective genes in diffuse large B-cell lymphoma (DLBCL) patients and to assess their prognostic values. Samples from 44 patients with DLBCL were evaluated using fluorescence in situ hybridization and immunohistochemical analyses. BCL6 was the most rearranged gene (63.6%), followed by MYC (31.8%), TP53 (22.7%), and BCL2 (18.2%). Multiple rearrangements were detected in 40.9% of the cases. BCL6 was the most expressed protein (78.6%), followed by TP53 (69.04%), BCL2 (59.5%) and MYC (14.3%). Expression of multiple proteins was detected in 67.4% of the cases. BCL2 (P = .003) expression had a significant negative influence on overall survival,whereas BCL6 (P = .014) expression had a significant positive influence. Our results with a different pattern of gene rearrangements and associated protein overexpression indicate the molecular genetic complexity of DLBCLs, which reflects the morphologic, biologic, and clinical heterogeneity of these lymphomas.

Ozet: Waldenstrom Makroglobulinemisi (WM) immunglobulin (Ig)M protein artisi ile karakterize lenfoplazmasitik bir lenfomadir. Anemi, trombositopeni, hepatosplenomegali (HSM), lenfadenopati (LAP) ve nadiren de hipervizkosite hastaligin klinik ozelliklerindendir. Yas, hemoglobin duzeyi, trombosit sayisi, beta-2 mikroglobulin ve monoklonal IgM miktari prognoz uzerine etkili faktorlerdendir. Hastalarimizin %84’unde HM, %47’inde SM ve %63’unde LAP saptandi. En sik basvuru semptomu %47,4 ile halsizlik, yorgunluktu. Hastalarimizin yaklasik yarisi yuksek risk skoruna sahip olup ortalama yasam sureleri 67 ay idi. ANAHTAR KELIMELER: Waldenstrom makroglobulinemisi, prognoz. CLINICAL CHARACTERISTICS AND PROGNOSIS OF PATIENTS WITH WALDENSTROM'S MACROGLOBULINEMIA: SINGLE CENTER EXPERIENCE Abstract: Waldenstrom’s Macroglobulinemia (WM) is a lymphoplasmacytic lymphoma associated with a monoclonal immunoglobulin (Ig)M protein. The clinical manifestations of the disorder are anemia, thrombocytopenia, hepato-splenomegaly (HSM), lymphadenopathy (LAP), and rarely hyperviscosity. Age, hemoglobin level, platelet count, beta-2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. The clinical manifestations in our patients were hepatomegaly 84%, splenomegaly 47%, and lymphadenopathy 63%. The most common presenting symptom was fatigue. Our patients’ risk scores were high and their overall survival was 67 months. KEY WORDS: Waldenstrom ‘s Macroglobulinemia, prognosis

Ozet: T hucreli prolenfositik losemi (T-PLL), nadir gorulen, agresif, matur, post-timik T hucreli bir neoplazidir. Olgularin %15’i tani sirasinda asemptomatiktir.57 yasinda erkek, sag alt ekstremitede agri nedenli derin ven trombusu saptanarak hematoloji poliklinigine yonlendirilen hastanin Hb 14,9 g/dl, beyaz kuresi 70800/mm3, absolu notrofil sayisi (ANS) 7400/mm3, absolu lenfosit sayisi (ALS) 55900/mm3, Platelet 250000/mm3 saptanan degerlendirilen periferik yaymasinda matur, kucuk, cogunda serebriform tarzda nukleus olan lenfositler izlendi. Flowsitometrik incelemesinde lenfosit kapisinda CD2(+), CD7(+), CD8(+), CD3(+) hucreler saptandi. Kemik iligi biyopsisinde diffuz olarak kucuk hiperkromatik nukleuslu dar sitoplazmali lenfoid karakterde hucre infiltrasyonu, bu hucreler CD2, CD3, CD5, CD7, CD8 ile yaygin pozitif saptanarak ‘T hucreli prolenfositik losemi’ tanisi konuldu. Hasta asemptomatik olmasi nedeni ile ‘indolen T-PLL’ kabul edilerek ilacsiz olarak takibe alindi. Fakat tani konulduktan 2 ay sonra semptomatik olmasi nedeni ile kemoterapi baslandi. Hasta septik sok ve hastalik progresyonu nedeni ile ex oldu. Anahtar Kelimeler: T-PLL, CD8(+). A RARE T-CELL LYMPHOID DISEASES: CD8 (+) T-CELL PROLYMPHOCYTIC LEUKEMIA Abstract: T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive, mature post-thymic T-cell neoplasia. It is asymptomatic in 15% of cases. 57-year-old male patient was directed to Hematology outpatient clinics due to right lower extremity deep vein thrombosis. Hb 14,9 g/dl, WBC 70800/mm3, ANC 7400/mm3, ALC 55900/mm3, platelet 250000/mm3. In blood smear; mature, small lymphocytes mostly having cerebriform type nucleus were seen; in flow-cytometric evaluation CD2(+), CD7(+), CD8(+), CD3(+) cells were detected. Bone marrow biopsy showed diffuse small hyper chromatic nuclei and a narrow cytoplasm of lymphoid character cell infiltration. These cells were found extensively positive with CD2, CD3, CD5, CD7 and CD8. He was diagnosed as “T-cell prolymphocytic leukemia”. Since he was asymptomatic, he was regarded as indolent T-PLL, and followed without any treatment. But after 2 months he was symptomatic and chemotherapy was began. The patient died due to septic shock and T-PLL progression Key Words: T-PLL, CD8(+)

OZET: Kanser hastalari, ortak risk faktorleri ya da onceki malignite tedavisinin karsinojenik etkisiyle diger maligniteler icin artmis risk tasirlar. Cogu malignite icin sagkalim oranlari arttigindan birden fazla malignitesi olan hasta sayisi da artmaktadir. Kronik lenfositik losemi (KLL) de solid tumor ve diger lenfoid malignitelerin riskinde artisla birliktelik gosterir fakat bu iliskinin mekanizmasi net degildir. Bu yazida KLL ve hematolojik olmayan maligniteli hastalarimizi geriye donuk olarak degerlendirdik. Hem KLL hem de hematolojik olmayan maligniteli 11 hastamiz mevcuttu. Hastalarin sadece klinik ve laboratuvar ozelliklerini degil sitogenetik sonuclarini da sunduk. Amacimiz bu hastalardaki nedensel faktorlerin rolune ve tedavi seceneklerine katki saglamaktir. ANAHTAR KELIMELER: Kronik lenfositik losemi, hematolojik olmayan malignite, risk faktorleri, sitogenetik SUMMARY: Cancer patients are often at increased risk for other malignancies due to shared risk factors or carcinogenecity of the treatment for prior malignancy. As survival rates for most malignancies are increasing, the number of patients with more than one malignancy is also increasing. In this report we evaluated our patients having both chronic lymphoytic leukemia (CLL) and a non-hematologic malignancy retrospectively. We had 11 patients having both CLL and a non-hematologic malignancy. We aimed to add new insights into the role of casual factors and treatment options by reporting our patients with CLL and a non-hematologic malignancy. KEYWORDS: Chronic lymphocytic leukemia, cytogenetics, non-hematologic malignancy, risk factors

Gumus E, Aras BD, Cilingir O, Yarar C, Carman KB, Laciner-Gurlevik S, Kocak O, Artan S. Apolipoprotein E allelic variants and cerebral palsy. Turk J Pediatr 2018; 60: 361-371. Cerebral palsy (CP) is the most frequent cause of mobility restriction and posture disturbance in childhood. Against the complexity in disease etiology, genetic factors, including Apolipoprotein E allelic distribution in this patient population, are worthy targets for investigation. ApoE is a lipoprotein of central nervous system encoded by ApoE gene with its 3 main co-dominant alleles, 2, 3 and 4. We aimed to evaluate the allelic frequencies of ApoE gene and its association with coexisting clinical entities such as vision and hearing impairment, cognitive problems, seizures and MRI findings in a pediatric patient population native to middle Anatolian region. Seventy-eight children with CP and 60 healthy controls were genotyped. Genotypic variations along with coexisting clinical conditions and CP-related medical findings were compared between the patient and control groups. The Denver Developmental Screening Test for all, the Wechsler Intelligence Scale for Children-IV (short form WISC-IV; Turkish version) for the patients > 6y and the Stanford-Binet Intelligence Scale (SB-5) for those who aged 2-6 years old were employed to evaluate cognitive and mental abilities of the patients. ApoE 2 and 4 alleles were more frequent in the patient group (p < 0.05), whereas ApoE 3 allele was more frequent in the healthy controls. ApoE 2/4 genotype has been determined 29% in the case group, but none in healthy control group. In the patient group with apolipoprotein 4 or 2 alleles, the rate of emergency cesarean section was found being significantly higher than the group with 3 allele. Brain MRI findings were not significantly different among ApoE allelic variants within the patient group. Our data show that the ApoE alleles may be effective in the development of cerebral palsy and may be associated with some clinical manifestations in those patients.

To determine the incidences of copy number aberrations of receptor kinases and their relations in Turkish patients with gastric adenocarcinoma. Materials and methods: The prevalence of genomic copy number aberrations of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2)/topoisomerase IIa (TOP2A), centrosome-associated kinase aurora A (AURK A), centrosome-associated kinase aurora B (AURK B), and mesenchymal-epithelial transition factor (MET) genes and polysomies of related chromosomes were analyzed by fluorescent in situ hybridization (FISH) in tumor samples from 35 patients with gastric cancer. Results: There were 28.6%, 65.7%, 20.0%, 17.1%, 60.0%, and 45.7% cases considered FISH-positive for EGFR, MET, HER2, TOP2A, AURK A, and AURK B genes, respectively. Statistically significant associations were determined in detection of amplifications of 1) EGFR gene with chromosome 7 polysomy, 2) MET gene in nonpolysomic chromosome 7 nuclei, 3) HER2/TOP2A genes in nonpolysomic chromosome 17 nuclei, 4) coamplification of HER2/TOP2A in poorly differentiated carcinomas, and 5) AURK A gene in nonpolysomic chromosome 20 nuclei. Most of the aberrations were predominantly seen in poorly differentiated tumors, but a high rate of the amplified MET gene was also detected in moderately differentiated carcinomas. Conclusion: Chromosome 7 polysomy may be responsible for EGFR gene amplifications, and we concluded that MET and AURK A genes amplifications were commonly seen aberrations in gastric adenocarcinomas and may offer information about disease progression and administration of individualized treatment for gastric cancer patients.