Tongue carcinoma infrequently harbor common actionable genetic alterations

BMC Cancer

Daniel SW Tan¹  Weining Wang³  Hui Sun Leong⁴  Pui Hoon Sew⁴  Dawn P Lau⁴  Fui Teen Chong⁴  Sai Sakktee Krisna⁴  Tony KH Lim²  N Gopalakrishna Iyer³ 

[1] Department of Medical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore

[2] Department of Pathology, Singapore General Hospital, Outram Road, Singapore 169610, Singapore

[3] Department of Surgical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore

[4] Cancer Therapeutics Research Laboratory, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore

关键词: HNSCC;    Oral cancers;    Sequenom;    Squamous cell carcinoma;    Therapeutic;    Druggable;   

Others  :  1121062
DOI  :  10.1186/1471-2407-14-679

 received in 2014-06-23, accepted in 2014-09-11,  发布年份 2014

【 摘 要 】

Background

Oral tongue squamous cell carcinomas (TSCC) are a unique subset of head and neck cancers with a distinct demographic profile, where up to half of the cases are never smokers. A small proportion of patients with OSCC are known to respond to EGFR TKI. We used a high-sensitivity mass spectrometry-based mutation profiling platform to determine the EGFR mutation status, as well as other actionable alterations in a series of Asian TSCC.

Methods

66 TSCC patients treated between 1998-2009 with complete clinico-pathologic data were included in this study. Somatic mutation profiling was performed using Sequenom LungCarta v1.0, and correlated with clinical parameters.

Results

Mutations were identified in 20/66(30.3%) of samples and involved TP53, STK11, MET, PIK3CA, BRAF and NRF2. No activating EGFR mutations or KRAS mutations were discovered in our series, where just over a third were never smokers. The most common mutations were in p53 (10.6%; n = 7) and MET (10.6%, n = 11) followed by STK11 (9.1%, n = 6) and PIK3CA (4.5%, n = 3). BRAF and NRF2 mutations, which are novel in TSCC, were demonstrated in one sample each. There was no significant correlation between overall mutation status and smoking history (p = 0.967) or age (p = 0.360). Positive MET alteration was associated with poorer loco-regional recurrence free survival (LRFS) of 11 months [vs 90 months in MET-negative group (p = 0.008)]. None of the other mutations were significantly correlated with LRFS or overall survival. Four of these tumors were propagated as immortalized cell lines and demonstrated the same mutations as the original tumor.

Conclusions

Using the Sequenom multiplexed LungCarta panel, we identified mutations in 6 genes, TP53, STK11, MET, PIK3CA, BRAF and NRF2, with the notable absence of EGFR and HER2 mutations in our series of Asian OSCC. Primary cell line models recapitulated the mutation profiles of the original primary tumours and provide an invaluable resource for experimental cancer therapeutics.

【 授权许可】

   
2014 Tan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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