The alterations found in our study supports the contribution of gene amplifications and indicate cooperation between certain oncogenes in the pathogenesis of HNSCC. Correlations between amplification of less familiar genes and known oncogenes warrant further investigation. This article is protected by copyright. All rights reserved.

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Squamous cell carcinoma of the head and neck (HNSCC) is among the most frequent cancers worldwide. The etiology and pathogenesis of HNSCC are influenced by multiple genetic factors in addition to environmental and lifestyle-related factors. However, the mechanism underlying the HNSCC is still far from clear.The membrane associated gene CT120 was previously identified from chromosome 17p13.3 as a lung cancer-associated gene. Its function as an activator of the Erk and Akt signaling pathways in human lung cancer cell lines suggested that CT120 has an oncogenic function. However, there is no data in the literature on the role of CT120 in any other cancer type. Therefore, the aim of this study was to determine the expression rate and probable function of CT120 in HNSCC.Tumor tissues from 50 patients were analyzed by real-time quantitative RT-PCR to investigate the expression rate and by direct sequencing to differentiate the CT120A and CT120B variants. CT120 overexpression was observed in 58% of tumors compared to non-cancerous tissue samples and this up-regulation was directly associated with the upregulation of the CT120A variant and with the stage of the disease (p=0.001).Our results indicate that the CT120 gene may function in the development of HNSCC.

Background: CT120 is a universally expressed protein with seven transmembrane domains. It functions in cell proliferation, survival and apoptosis by activating Raf/MEK/ERK and PI3K/Akt signaling pathways. Evidence suggests that CT120 plays important roles in lung carcinogenesis and oncogenic pathway activation. c-Myc is an important transcription factor modulating cell progression, apoptosis and cellular transformation. Previous studies have shown that MYC gene is amplified in many types of cancer including head and neck squamous cell carcinoma (HNSCC). Myc can regulate expression of many genes by binding to E-boxes. The aim of this study was to investigate the relationship between c-Myc protein and CT120 gene.Methods: Tumor and normal tissue samples from 50 patients with HNSCC were investigated with chromatin immunoprecipitation assay (ChIP), Illumina MiSeq, bisulphite sequencing and qRT-PCR.Results: c-Myc binds to all E-boxes except E-box 5 on CT120 promoter. The CpG dinucleotides were found to be partially methylated in all tumor and normal tissue samples. Bisulphite sequencing showed a 10% down-regulation in the methylation levels of the tumor tissues. CT120 gene was hypomethylated and up-regulated in 56% of the tumor tissue samples. Expression of c-Myc was significantly higher in tumor tissues than in non-cancerous tissue samples. MYC was overexpressed in 68% of the tumor tissue samples compared to normal tissues. The mean MYC levels were 2.42-fold higher in the tumor tissue samples. In 48% of the tumor tissues, MYC and CT120A mRNA were up- or down-regulated simultaneously (p<0.001).Conclusion: We show that CT120 gene is a target of c-Myc and it contributes to cancer progression in HNSCC.

HNSCC is the sixth most common form of cancer and represents the third common cause of cancer-related deaths worldwide. Therefore, there is a need to understand the molecular mechanisms involved in the pathogenesis of HNSCC. The c-myc protein belongs to the myc family of transcription factors and plays a fundamental role in cell cycle progression, apoptosis and cellular transformation. In the human genome, the MYC gene is located on chromosome 8 and its protein product regulates expression of 15% of all genes through binding to the Enhancer box (E-box) sequences. An E-box is a DNA sequence found in the promoter regions of eukaryotic genes that acts as a protein binding site to regulate gene expression. The CANNTG consensus sequence of the E-box is known as the canonical E-boxes. There are several other non-canonical E-box motifs such as the GATGTG, CATGCG, CACGCG, CACGAG, CGCGAG and CAACGTG sequences. Amplification of the MYC gene is observed in many different types of cancers including HNSCC. CT120 is a novel gene which encodes a human trans-membrane plasma protein. It has been shown that up-regulation of CT120 is associated with lung and head and neck carcinogenesis. In this study we investigated the promoter region of the CT120 gene and identified 6 E-boxes. To test whether c-myc binds to these E-boxes we performed chromatin immunoprecipitation (ChIP) assays. We demonstrated that c-myc binds strongly to the E-boxes 2, 3 and 4. It is well known that the expression rates of the genes are under the control of epigenetic modifications. Methylation of the CpG islands which are found in the promoter regions is one of the most studied epigenetic modifications. We identified two putative CpG islands in the promoter of the CT120 gene. To investigate the possible epigenetic regulation of CT120 and the effect of the promoter methylation to the binding of c-myc, we also investigated the methylation levels of the two islands in the CT120 promoter by MS-PCR. We observed a slight decrease (3.1%) in the methylation level of the first CpG-rich region. In 56% (28/50) of the tumor tissues methylation was decreased compared to the non-cancerous tissues. However, there was no statistically significant correlation between the promoter methylation and CT120 mRNA level. Depending on these data we investigated the expression levels of the c-myc and CT120 in the 50 HNSCC and normal tissue samples by qRT-PCR and observed a direct correlation between the overexpression of the c-myc and CT120 genes. Overexpression of CT120 and c-myc were observed in 29 (58%) and 34 (68%) of the tumors, respectively, compared to non-cancerous tissues. A total of 24 (48%) patients out of 50 showed a concurrent pattern of either up- or down regulation. Our results indicate that the CT120 gene is a target of c-myc and that both proteins may participate in the progression of HNSCC. Citation Format: Onur Baykara, Elif Baltaci, Betul Seyhan, Nejat Dalay, Nur Buyru. Regulation of CT120 gene as a new target of c-myc in head and neck squamous cell carcinoma (HNSCC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1132.

Brain tumors without giving neurological symptoms yet; it can also occur with a wide range of psychiatric symptoms such as anxiety, panic attacks, depression, eating disorders, personality change, vision hallucinations and mania. Unfortunately, the diagnosis of brain tumor might be delayed in patients whose clinical symptoms are like these. Brain imaging techniques should be performed especially in patients who don't respond to psychiatric drug treatment and have no neurological symptoms. In this article, a female patient who presented to our psychiatry outpatient clinic with symptoms of depression, accompanied by psychosis symptoms in later periods, and whose mass was detected as a result of magnetic resonance imaging, is discussed in the light of literature studies. Here, we aimed to emphasize the importance of neurological examination and brain imaging methods in patients who come to psychiatry especially with atypical symptoms.

Bulgular: Kadınlarda, erkeklere göre depresyon, anksiyete, obsesif kompulsif bozukluk, uykusuzluk ve sağlık anksiyetesi ölçek skorları daha yüksek saptandı. Ancak sadece anksiyete ve OKB ölçeklerinde kadınlarda, erkeklere göre istatiksel olarak anlamlı bir farklılık saptandı (p=0.021, p=0.005). Post-hoc analiz sonuçlarına göre, anksiyete, depresyon ve uyku bozukluğu belirtilerinden yüksek skorlar hemşirelerde, sonra doktorlarda yüksek bulunmuş olup diğer sağlık çalışanlarında ise en düşüktü. Sonuç: Çalışmamız; depresyon, uykusuzluk, anksiyete belirtilerinin cinsiyet ve meslek alt tipleri arasında anlamlı farklılıklar olduğunu göstermiştir. Bu sebeple, sağlık çalışanlarının ruhsal yakınmalarına yönelik sağlık uygulamalarında sosyo-demografik farklılıkların da göz önünde bulundurulması faydalı olabilir. Ayrıca yıllar sonra yeniden pandemi gerçeği ile karşı karşıya gelen sağlık çalışanlarının, ruh sağlığını göz önünde bulundurmanın gerekliliğini ve önemini vurgulamaktayız.

Gene amplification is a common finding in a broad spectrum of tumor types, often leading to increased levels of gene expression, a mechanism by which genetic changes contribute to the initiation or progression of cancer. HNSCC is among the neoplasias that frequently show amplification of specific genomic regions. Previous cytogenetic and molecular genetic studies by Fluorescence in situ Hybridization (FISH) and comperative genome hybridization (CGH) and other molecular methods showed that frequently amplified chromosomal regions in primary HNSCC tumors are 3q, 8q, 8p, 11q, 9q. Generally, proto-oncogenes reside in these amplified regions and amplification of these often leads to increased levels of gene expression. Therefore, in this study we investigated amplification of 22 different oncogenes mapping to these regions. The analyses were performed by MLPA on an ABI 3100 genetic analyzer and relative peak areas of the amplification products were evaluated using the Coffalyser MLPA analysis software. Analysis of 50 HNSCC tumor tissue samples showed that the most frequently amplified genes were from the regions 17q12 (MED1), 11q13.3 (CCND1), 8q (MYC and MTDH) and 8p (ZNF703) with frequencies of 24%, 24%, 20%, 20% and 18%, respectively. In total, Copy Number Alterations of the CCND1 and MED1 genes were observed in 12 of 50 tumor samples. For the CCND1 gene 6 of these alterations were heterozygous duplications and the remaining 6 were triplications. On the other hand, for the MED1 gene duplications were observed in 8 samples and trriplications were detected in 4 samples. Triplication of the MTDH gene was not observed in any of the amplified samples. However, one third of the ZNF703 amplifications were triplications. Amplification of the CCND1 and MYC genes are frequently observed in different types of cancers including HNSCC. More recently overexpression of MTDH has been associated with lymph node metastasis and poor-survival in HNSCC. However, to our knowledge there is no data in the literature investigating the ZNF703 gene in HNSCC. Our data indicate that ZNF703 may represent a candidate gene the role of which warrants more detailed analysis in HNSCC. Citation Format: Nejat Dalay, Orkun Gurbuz, Elif Baltaci, Emin Karaman, Nur Buyru. Analysis of copy number changes in HNSCC by MLPA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4922. doi:10.1158/1538-7445.AM2015-4922