RGD Reference Report - Exome Sequencing of Oral Squamous Cell Carcinoma Reveals Molecular Subgroups and Novel Therapeutic Opportunities. - Rat Genome Database

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Exome Sequencing of Oral Squamous Cell Carcinoma Reveals Molecular Subgroups and Novel Therapeutic Opportunities.

Authors: Su, Shih-Chi  Lin, Chiao-Wen  Liu, Yu-Fan  Fan, Wen-Lang  Chen, Mu-Kuan  Yu, Chun-Ping  Yang, Wei-En  Su, Chun-Wen  Chuang, Chun-Yi  Li, Wen-Hsiung  Chung, Wen-Hung  Yang, Shun-Fa 
Citation: Su SC, etal., Theranostics. 2017 Feb 26;7(5):1088-1099. doi: 10.7150/thno.18551. eCollection 2017.
RGD ID: 151347687
Pubmed: PMID:28435450   (View Abstract at PubMed)
PMCID: PMC5399578   (View Article at PubMed Central)
DOI: DOI:10.7150/thno.18551   (Journal Full-text)

Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic strategies and tailored treatment options is an unmet need. To unveil the mutational spectrum, whole-exome sequencing of 120 OSCC from male individuals in Taiwan was conducted. Analyzing the contributions of the five mutational signatures extracted from the dataset of somatic variations identified four groups of tumors that were significantly associated with demographic and clinical features. In addition, known (TP53, FAT1, EPHA2, CDKN2A, NOTCH1, CASP8, HRAS, RASA1, and PIK3CA) and novel (CHUK and ELAVL1) genes that were significantly and frequently mutated in OSCC were discovered. Further analyses of gene alteration status with clinical parameters revealed that the tumors of the tongue were enriched with copy-number alterations in several gene clusters containing CCND1 and MAP4K2. Through defining the catalog of targetable genomic alterations, 58% of the tumors were found to carry at least one aberrant event potentially targeted by US Food and Drug Administration (FDA)-approved agents. Strikingly, if targeting the p53-cell cycle pathway (TP53 and CCND1) by the drugs studied in phase I-III clinical trials, those possibly actionable tumors are predominantly located in the tongue, suggesting a better prediction of sensitivity to current targeted therapies. Our work revealed molecular OSCC subgroups that reflect etiological and prognostic correlation as well as defined the landscape of major altered events in the coding regions of OSCC genomes. These findings provide clues for the design of clinical trials for targeted therapies and stratification of OSCC patients with differential therapeutic efficacy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
oral squamous cell carcinoma onsetIAGP 151347687DNA:mutations:multipleRGD 
oral squamous cell carcinoma onsetISOFAT1 (Homo sapiens)151347687; 151347687DNA:mutations:multipleRGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Neoplasm of the oral cavity onsetIAGP 151347687DNA:mutations:multipleRGD 
Objects Annotated

Genes (Rattus norvegicus)
Fat1  (FAT atypical cadherin 1)

Genes (Mus musculus)
Fat1  (FAT atypical cadherin 1)

Genes (Homo sapiens)
FAT1  (FAT atypical cadherin 1)


Additional Information