Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma
Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma
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DOI：
10.1038/modpathol.2017.128
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发表时间：
2018-02-01
期刊：
影响因子：
7.5
通讯作者：
Gupta, Ruta
中科院分区：
文献类型：
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作者：
Zilberg, Catherine;Lee, Matthew Weicai;Gupta, Ruta
皮肤鳞状细胞癌是第二种最常见的恶性肿瘤，最常发生在头颈部(头颈部皮肤鳞状细胞癌)。局部晚期或转移性疾病的治疗与功能障碍和毁容有关。人们对潜在的遗传机制知之甚少。对从福尔马林固定和石蜡包埋的高危原发头颈部皮肤鳞状细胞癌中提取的DNA进行了48个临床相关基因的定向测序，这些人在至少24个月的随访中仍然没有转移。对体细胞突变与临床病理特征的相关性进行评估，并与转移性疾病文献中所描述的进行比较。确定了44个与癌症相关的基因的变化。TP53基因突变占100%，APC、ATM、ERBB4、GNAQ、KIT、RB1和ABL1基因突变占60%。FGFR2突变(40%)仅见于有神经侵袭的患者。MLH1突变仅见于两名较年轻的患者(
Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (