Unfortunately, despite advances in detection and treatment, 5-year overall survival (OS) rates for OTSCC remain alarmingly low. Current treatment strategies involve a multimodality approach involving surgery, chemotherapy, and radiotherapy. Of these, two-thirds are oral tongue squamous cell carcinoma (OTSCC). Oral squamous cell carcinoma (OSCC) accounts for 270,000 new cancer cases and 145,000 deaths annually, the majority of which occur in developing countries. We also observed somatic mutations in multiple therapeutically relevant genes, which may represent candidate drug targets in this highly lethal tumor type. Patients harboring mutations in actionable pathways were more likely to succumb from recurrent disease compared with those who did not, suggesting that the former should be considered for treatment with targeted compounds in future trials.ConclusionsOur study defines the Asian OTSCC mutational landscape, highlighting the key role of Notch signaling in oral tongue tumorigenesis. A high proportion of OTSCCs also presented with alterations in drug targetable and chromatin remodeling genes. Importantly, these Notch pathway alterations were prognostic on multivariate analyses.
Despite a lack of previously reported NOTCH1 mutations, integrated analysis showed enrichments of alterations affecting Notch signaling in OTSCC. Here, we sought to characterize the OTSCC genomic landscape and to determine factors that may delineate the genetic basis of this disease, inform prognosis and identify targets for therapeutic intervention.MethodsSeventy-eight cases were subjected to whole-exome (n = 18) and targeted deep sequencing (n = 60).ResultsWhile the most common mutation was in TP53, the OTSCC genetic landscape differed from previously described cohorts of patients with head and neck tumors: OTSCCs demonstrated frequent mutations in DST and RNF213, while alterations in CDKN2A and NOTCH1 were significantly less frequent. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing incidence in younger patients, females and never-smokers. These findings may be used as part of marker-assisted selection in tilapia breeding programmes.BackgroundCarcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival.
Genotypes with higher additive genetic values for weight were identified in the Chitralada strain, suggesting a possible impact of these additive effects of the GH SNP genotype on the growth rate of Nile tilapia. Single nucleotide polymorphisms 6-10 were also found to be significantly associated with growth ( p-value < .05). In all weight recordings, five genotype blocks were significantly associated with the highest weights. A total of 10 SNPs were identified, nine in the proximal promoter and one located in the 5′ UTR, forming 10 genotype blocks. Association between SNPs and growth rate was statistically evaluated using a univariate linear mixed model that included both fixed and random effects. Genotype blocks or sets of SNP genotypes and frequencies were also estimated. Allele and genotype frequencies were estimated for each SNP and genotype. The targeted regions were amplified, sequenced, aligned and screened for the presence of SNPs thereafter, performance tests were used to check for the association between SNPs and weight. The present study aimed to identify single nucleotide polymorphisms (SNPs) in GH gene regions to evaluate the association of SNP variations with the growth rate of two Nile tilapia: Oreochromis niloticus (Linnaeus, 1758) strains. Polymorphisms in the growth hormone (GH) gene that is associated with the growth rate of farmed fish have been the target of many breeding programmes.
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