Somatic copy number alterations detected by ultra-deep targeted sequencing predict prognosis in oral cavity squamous cell carcinoma

Abstract

BackgroundUltra-deep targeted sequencing (UDT-Seq) has advanced our knowledge on the incidence and functional significance of somatic mutations. However, the utility of UDT-Seq in detecting copy number alterations (CNAs) remains unclear. With the goal of improving molecular prognostication and identifying new therapeutic targets, we designed this study to assess whether UDT-Seq may be useful for detecting CNA in oral cavity squamous cell carcinoma (OSCC).MethodsWe sequenced a panel of clinically actionable cancer mutations in 310 formalin-fixed paraffin-embedded OSCC specimens. A linear model was developed to overcome uneven coverage across target regions and multiple samples. The 5-year rates of secondary primary tumors, local recurrence, neck recurrence, distant metastases, and survival served as the outcome measures. We confirmed the prognostic significance of the CNA signatures in an independent sample of 105 primary OSCC specimens.ResultsThe CNA burden across 10 targeted genes was found to predict prognosis in two independent cohorts. FGFR1 and PIK3CAamplifications were associated with prognosis independent of clinical risk factors. Genes exhibiting CNA were clustered in the proteoglycan metabolism, the FOXO signaling, and the PI3K-AKT signaling pathways, for which targeted drugs are already available or currently under development.ConclusionsUDT-Seq is clinically useful to identify CNA, which significantly improve the prognostic information provided by traditional clinicopathological risk factors in OSCC patients.

Identification of hallmarks of lung adenocarcinoma prognosis using whole genome sequencing

“…Sequencing has presented advance in detection of biomarkers to progression of various cancers. By whole genome sequencing (WGS) or target sequencing, some studies have demonstrated the prognostic prediction role of high copy number alteration burden in the prostate cancer relapse [ 15 ], FGFR1 and PIK3CA amplifications in oral cavity squamous cell carcinoma [ 16 ], and MYC amplification in pancreatic adenosquamous carcinoma and lung adenocarcinomas [ 17 , 18 ].…”

Introduce a New Approach to Detect Genes Associated to Oral Squamous Cell Carcinoma

“…Epstein-Barr virus infection was reported statistically associated with increased risk of OSCC [44]. Peng et al found that copy number alterations in OSCC were distributed in the proteoglycan metabolism pathway [45]. The Bacterial invasion of epithelial cells pathway has not been reported its relation with OSCC yet.…”

Expression of FGF‐2/FGFR‐1 in normal mucosa, salivary gland, preneoplastic, and neoplastic lesions of the oral cavity

“…In regard to the FGFR‐1 gene amplification assessed by FISH, it predicts prognosis and was associated with distant metastasis in a study with 310 patients with OSCC . Similarly, FGFR1 amplification was found only in 10% of 133 OSCC cases and in 5.6% of oropharyngeal SCC .…”

“…Fibroblast growth factor 2 expression and FGFR-1 expression have been correlated with poorer differentiation, higher invasion potential, and worse prognosis in OSCC patients, 1,10,12,[40][41][42][43][44][45] besides influencing the epithelial-mesenchymal transition (EMT) in OSCC cell lines. 11,46 Furthermore, the expression of FGF-2 and FGFR-1 in fibroblasts at the invasive front of OSCC was correlated with more invasive cases, lymph node metastasis, and poor prognosis.…”