Targeted molecular characterization of external auditory canal squamous cell carcinomas.
Targeted molecular characterization of external auditory canal squamous cell carcinomas.
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DOI：
10.1002/lio2.654
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发表时间：
2021-10
影响因子：
1.9
通讯作者：
Brenner JC
中科院分区：
文献类型：
--
作者：
Basura GJ;Smith JD;Ellsperman S;Bhangale A;Brenner JC
外耳道鳞状细胞癌（SCC）可能具有独特的基因组改变，可以解释侵略性行为，并区分这些肿瘤从皮肤SCC的其他子网站。EAC SCC出现在头部和颈部的非紫外线暴露区域，通常具有局部侵袭性，并可能转移到淋巴结或远处部位。其他部位皮肤SCC的基因组改变已得到充分证实;然而，EAC SCC的突变特征尚不清楚，可能导致独特的解剖部位、高复发率和肿瘤扩散。我们对一组原发性EAC SCC进行了靶向测序，以鉴定复发的和潜在的靶向基因组改变。从7例EAC SCC的福尔马林固定石蜡包埋标本中提取基因组DNA，并使用227个基因组进行靶向DNA测序。使用我们经过验证的内部生物信息学管道注释体细胞改变和基因拷贝数改变。在我们的EAC SCC中，我们发现TP 53和受体酪氨酸激酶（例如EGFR、FGFR）和PI 3 K通路（例如PIK 3CA）基因的复发性改变，与其他头颈部皮肤SCC相似。我们还观察到端粒酶逆转录酶扩增和DNA甲基转移酶1改变的高频率，这两种情况在其他部位的皮肤SCC中很少观察到。这些数据代表了对EAC SCC进行精确分子表征的第一步，这可能会导致对肿瘤生物学的更深入理解和针对独特肿瘤的现代化精准医学方法。证据等级：NA
Squamous cell carcinomas (SCC) of the external auditory canal (EAC) may harbor unique genomic alterations that may explain aggressive behavior and differentiate these tumors from cutaneous SCCs of other subsites. EAC SCCs arise in a non‐ultraviolet‐exposed region of the head and neck, are often locally aggressive and may metastasize to lymph nodes or distant sites. The genomic alterations underlying cutaneous SCC of other sites are well‐documented; however, mutational profiles of EAC SCC are less well characterized and may contribute to the unique anatomic site, high rates of recurrence and tumor spread. We performed targeted sequencing of a cohort of primary EAC SCCs to identify recurring and potentially targetable genomic alterations. Genomic DNA was extracted from formalin‐fixed paraffin‐embedded specimens of 7 EAC SCCs and subjected to targeted DNA sequencing using a 227‐gene panel. Somatic alterations and gene copy number alterations were annotated using our validated, in‐house bioinformatics pipelines. In our EAC SCCs, we found recurrent alterations in TP53 and genes of receptor tyrosine kinase (eg, EGFR, FGFR) and PI3K pathways (eg, PIK3CA), similar to cutaneous SCCs of other head and neck sites. We also observed a high frequency of telomerase reverse transcriptase amplification and DNA methyltransferase 1 alterations, both of which are rarely observed in cutaneous SCCs of other sites. These data represent the first step toward precise molecular characterization of EAC SCCs that may lead to an enhanced understanding of tumor biology and modernized precision medicine approaches for unique tumors. Level of Evidence: NA
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DOI：
10.1158/1078-0432.ccr-14-1773
发表时间：
2015-03-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Li YY;Hanna GJ;Laga AC;Haddad RI;Lorch JH;Hammerman PS
通讯作者：
Hammerman PS
DNA甲基转移酶及其在肿瘤发生中的作用
影响因子：
11.1
作者：
Zhang W;Xu J
通讯作者：
Xu J
影响因子：
--
作者：
Gaudet, Jacques E.;Walvekar, Rohan R.;Lin, James
通讯作者：
Lin, James
影响因子：
0.9
作者：
Birkeland, Andrew C.;Burgin, Sarah J.;Brenner, J. Chad
通讯作者：
Brenner, J. Chad
影响因子：
50.3
作者：
Dotto GP;Rustgi AK
通讯作者：
Rustgi AK