The cancer of the oral floor

Rezumat. Tumorile maligne ale planșeului bucal ocupă locul al doilea între cancerele cavității orale, fiind situat procentual foarte aproape de cancerul limbii. Reprezintă cca. 25-30% din localizările cancerului oral și 2% din totalul cancerelor umane. Apare în special la bărbați, dupa vîrsta de 45 de ani. În dezvoltarea cancerului mucoasei cavităţii bucale cel mai important rol îl are tabagismul, fumătorii avînd un risc de 30 de ori mai mare de a face un cancer al mucoasei cavităţii bucale. Are importanţă consumul cronic de alcool, în cantităţi mari, infecţia cu HPV, patologia cronică dentară. Exista în prezent dovezi certe ale unei incidente crescute a cancerului oral la pacienții imunosupresați. Formele clinice de creştere ale cancerului mucoasei orale sînt: • ulcerativă, • nodulară • fisurală Cel mai frecvent întîlnite sînt formele de creştere ulcerativă şi fisurală. Clinic, tumora poate evolua în 2 direcții, și anume: ulcero-distructiv sau ulcero-vegetant. Forma ulcero-vegetantă sau proliferativă se prezintă ca o ulcerație acoperită de muguri cărnoși, brăzdați de fisuri și acoperiți de un strat superficial cu aspect granulativ. Forma ulcero-distructivă are o tendință marcată de invazie loco-regională și se prezintă ca o ulcerație cu margini anfractuoase, cu baza îndurată, cu fundul ulcerației murdar, acoperit de țesut granulativ și zone necrotice. Tratament. Scopul tratamentului multimodal complex în tumorile maligne oro-maxilo-faciale urmărește 2 deziderate majore, și anume: 1) perioada de supraviețuire să fie cît mai lungă; 2) asigurarea calității vieții, fapt realizat prin plastia reconstructivă imediată sau tardivă, care va favoriza reintegrarea bolnavului cît mai rapid în societate, precum și restabilirea și reabilitarea precoce a disfuncțiilor postchirurgicale. Tratamentul multimodal complex include, în funcție de stadializare, starea generală și opțiunea bolnavului, prioritățile fie de etapa chirurgicală asociată cu radio–, chimio–, imunoterapia, fie posibilitatea reconversiei tumorale și/sau a tratamentului paliativ radio–, chimio– și imunoterapic urmat sau nu de intervenția chirurgicală. În general, conform statisticilor U.I.C.C., rata de supraviețuire în tumorile maligne ale planșeului bucal, după tratamentul multimodal complex, este relativ mică. În T1 este de cca. 68%, în T2 de 42%, iar în T3 este sub 11%. Avînd în vedere aceste statistici sumbre, credem că depistarea precoce, alături de radicalitatea intervenției, în contextul unui tratament multimodal complex, ar mări șansele de supraviețuire ale acestor bolnavi.Summary. Malignant tumors of the floor of the mouth are on the second place among the oral cavity cancers. Localizations are about 25-30% of oral cancer and 2% of human cancers. It occurs mostly in men over the age of 45 years. Smoking has a important role in the development of buccal mucosa cancer. Smokers have a risk 30 times more likely to develop cancer of the oral mucosa. Chronic alcohol consumption is important în large quantities, HPV infection, and chronic dental pathology. There is now clear evidence of an increased incidence of oral cancer in immunosuppressed patients. Clinical forms of oral mucosa cancer growth are: • ulcerative • nodular • fissural The most commonly encountered forms of growth are ulcerative and fisssural. Clinically, the tumor can develop in two directions, namely: ulcerative or ulcerative destructive. Proliferative ulcerative form presents as an ulcer covered with fleshy buds, crossed by cracks and cover a surface layer with grain appearance. Ulcerative destructive form has a marked tendency to invade locally and represents an ulcer, with ulceration covered with granulation tissue and necrotic areas. Treatment. Purpose of complex multimodal treatment of malignant tumors of oro-maxillofacial follows two major goals, namely: 1) increase survival time 2) improve quality of life, which is achieved by immediate or delayed reconstructive plastic surgery, which will help the patient reintegrate into society as quickly and early recovery and rehabilitation of post surgical dysfunction. Complex multimodal treatment includes, according to staging and overall patient choice, or priorities associated with radio-surgical stage, chemotherapy, immunotherapy or retraining opportunity tumor and / or palliative treatment of radio-, chemo-and immunotherapy followed or no by surgery. Generally, as shown by UICC, the survival rate în malignant tumors of the floor of the mouth after multimodal treatment complex is relatively small. The T1 is about 68%, 42% in T2 and T3 is below 11%. Given these grim statistics, we believe that early detection, with radical surgery, in the context of a complex multimodal treatment would increase the chances of survival of these patients

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing