A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence

Reis, Patrícia P.; Waldron, Levi; Perez-Ordonez, Bayardo; Pintilie, Melania; Galloni, Natalie Naranjo; Yao, Xuan; Cervigne, Nilva K.; Warner, Giles; Mäkitie, Antti; Simpson, Craig D.; Goldstein, David P.; Brown, Dale; Gilbert, Ralph W.; Gullane, Patrick; Irish, Jonathan C.; Jurišica, Igor; Kamel‐Reid, Suzanne

doi:10.1186/1471-2407-11-437

Cited by 125 publications

(114 citation statements)

References 45 publications

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“…Microarray-based expression profiling of unmatched normal mucosa, primary tumors, lymph node metastases, and recurrent HNSCC lesions identified mRNA expression signatures predictive of metastasis and recurrence, but the clinical impact of these observations remains unrealized (20)(21)(22)(23). Only one study included analysis of patientmatched index primary tumors and synchronous nodal metastases; this found that the expression profiles of primary tumors were largely preserved in their respective metastatic lymph nodes (23).…”

Section: Introductionmentioning

confidence: 99%

Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma

Hedberg¹,

Goh²,

Chiosea³

et al. 2015

Journal of Clinical Investigation

154

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BACKGROUND.Recurrence and/or metastasis occurs in more than half of patients with head and neck squamous cell carcinoma (HNSCC), and these events pose the greatest threats to long-term survival. We set out to identify genetic alterations that underlie recurrent/metastatic HNSCC. METHODS.Whole-exome sequencing (WES) was performed on genomic DNA extracted from fresh-frozen whole blood and patient-matched tumor pairs from 13 HNSCC patients with synchronous lymph node metastases and 10 patients with metachronous recurrent tumors. Mutational concordance within and between tumor pairs was used to analyze the spatiotemporal evolution of HNSCC in individual patients and to identify potential therapeutic targets for functional evaluation.RESULTS. Approximately 86% and 60% of single somatic nucleotide variants (SSNVs) identified in synchronous nodal metastases and metachronous recurrent tumors, respectively, were transmitted from the primary index tumor. Genes that were mutated in more than one metastatic or recurrent tumor, but not in the respective primary tumors, include C17orf104, inositol 1,4,5-trisphosphate receptor, type 3 (ITPR3), and discoidin domain receptor tyrosine kinase 2 (DDR2). Select DDR2 mutations have been shown to confer enhanced sensitivity to SRC-family kinase (SFK) inhibitors in other malignancies. Similarly, HNSCC cell lines harboring endogenous and engineered DDR2 mutations were more sensitive to the SFK inhibitor dasatinib than those with WT DDR2. CONCLUSION.In this WES study of patient-matched tumor pairs in HNSCC, we found synchronous lymph node metastases to be genetically more similar to their paired index primary tumors than metachronous recurrent tumors. This study outlines a compendium of somatic mutations in primary, metastatic, and/or recurrent HNSCC cancers, with potential implications for precision medicine approaches. FUNDING.

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Section: Introductionmentioning

confidence: 99%

Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma

Hedberg¹,

Goh²,

Chiosea³

et al. 2015

Journal of Clinical Investigation

154

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“…ITGA2, ITGA3 and ITGAV, members of the integrins, are invasion-related genes (28,29). Integrins are transmembrane adhesion molecules that mediate cell-cell and cell-extracellular matrix attachment.…”

Section: Discussionmentioning

confidence: 99%

Expression profiles of microRNAs and their target genes in papillary thyroid carcinoma

Liu

Hou

et al. 2013

Oncology Reports

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Abstract. The incidence of thyroid cancer has recently experienced a rapid increase in China, and papillary thyroid carcinoma (PTC) accounts for nearly 80% of human thyroid cancers. In the present study, the differential expression of microRNAs (miRNAs) and their target genes were identified in order to analyze the potential roles of miRNAs as biomarkers and in papillary thyroid carcinogenesis. One hundred and twenty-six PTC samples were collected from patients at the China-Japan Union Hospital, China, and the gene/miRNA expression profiles were examined with Illumina BeadChips and verified by real-time RT-PCR. Gene Ontology (GO) categories were determined, and pathway analysis was carried out using KEGG. miRNA target genes were predicted by implementing three computational analysis programs: TargetScanS, DIANA-microT and PicTar. Two hundred and forty-eight miRNAs and 3,631 genes were found to be significantly deregulated (gene, P<0.05; miRNA, P<0.01) in PTC tissues when compared with their matching normal thyroid tissues. hsa-miR-206 (target gene, MET), hsa-miR-299-3p (target gene, ITGAV), hsa-miR-101 (target gene, ITGA3), hsa-miR-103 (target gene, ITGA2), hsa-miR-222 (target genes, KIT and AXIN2), hsa-miR-15a (target genes, AXIN2 and FOXO1) and hsa-miR-221 (target gene, KIT) were identified. Together with the functions of the target genes, we further elucidated the role of miRNAs in papillary thyroid carcinogenesis and suggest the use of miRNAs as biomarkers for early diagnosis. Our findings provide the basis for future studies in the field of miRNA-based cancer therapy.

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“…Expression datasets of human cell line were excluded in the study. The included GEO datasets (GSE) are shown in Table 1 (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35).…”

Section: Methodsmentioning

confidence: 99%

Expression and influence of Notch signaling in oral squamous cell carcinoma

Osathanon

Nowwarote

Pavasant

2016

Journal of Oral Science

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A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence

Cited by 125 publications

References 45 publications

Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma

Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma

Expression profiles of microRNAs and their target genes in papillary thyroid carcinoma

Expression and influence of Notch signaling in oral squamous cell carcinoma

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