Chan Jason Y K, Poon Peony Hiu Yan, Zhang Yong, Ng Cherrie W K, Piao Wen Ying, Ma Meng, Yip Kevin Y, Chan Amy B W, Lui Vivian Wai Yan
Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
F1000Res. 2018 Apr 26;7:499. doi: 10.12688/f1000research.14383.1. eCollection 2018.
Soft tissue sarcoma of the tongue represents a very rare head and neck cancer with connective tissue features, and the genetics underlying this rare cancer are largely unknown. There are less than 20 cases reported in the literature thus far. Here, we reported the first whole-exome characterization (>×200 depth) of an undifferentiated sarcoma of the tongue in a 31-year-old male. Even with a very good sequencing depth, only 19 nonsynonymous mutations were found, indicating a relatively low mutation rate of this rare cancer (lower than that of human papillomavirus (HPV)-positive head and neck cancer). Yet, among the few genes that are somatically mutated in this HPV-negative undifferentiated tongue sarcoma, a noticeable deleterious frameshift mutation (with a very high allele frequency of >93%) of a gene for DNA replication and repair, namely (DNA polymerase delta interacting protein 2), and two recurrent mutations of the adipogenesis and adipocyte differentiation gene (retinol saturase), were identified. Thus, somatic events likely affecting adipogenesis and differentiation, as well as potential stem mutations to , may be implicated in the formation of this rare cancer. This identified somatic whole-exome sequencing profile appears to be distinct from that of other reported adult sarcomas from The Cancer Genome Atlas, suggesting a potential unique genetic profile for this rare sarcoma of the tongue. Interestingly, this low somatic mutation rate is unexpectedly found to be accompanied by multiple tumor protein p53 and germline mutations of the patient's blood DNA. This may explain the very early age of onset of head and neck cancer, with likely hereditary predisposition. Our findings are, to our knowledge, the first to reveal a unique genetic profile of this very rare undifferentiated sarcoma of the tongue.
舌部软组织肉瘤是一种极为罕见的具有结缔组织特征的头颈癌，这种罕见癌症的遗传学基础在很大程度上尚不清楚。迄今为止，文献报道的病例不足20例。在此，我们报告了一名31岁男性舌部未分化肉瘤的首个全外显子特征分析（深度>×200）。即便测序深度很高，也仅发现了19个非同义突变，表明这种罕见癌症的突变率相对较低（低于人乳头瘤病毒（HPV）阳性的头颈癌）。然而，在这种HPV阴性的未分化舌部肉瘤中发生体细胞突变的少数基因中，鉴定出了一个DNA复制和修复基因（即DNA聚合酶δ相互作用蛋白2）的明显有害移码突变（等位基因频率非常高，>93%），以及脂肪生成和脂肪细胞分化基因（视黄醇饱和酶）的两个复发性突变。因此，可能影响脂肪生成和分化的体细胞事件以及可能发生的基因干性突变，可能与这种罕见癌症的形成有关。所确定的体细胞全外显子测序图谱似乎与癌症基因组图谱中其他报道的成人肉瘤不同，提示这种罕见的舌部肉瘤可能具有独特的基因特征。有趣的是，意外发现这种低体细胞突变率伴随着患者血液DNA中多个肿瘤蛋白p53和种系突变。这可能解释了头颈癌发病年龄极早且可能存在遗传易感性的原因。据我们所知，我们的研究结果首次揭示了这种极为罕见的舌部未分化肉瘤的独特基因特征。
