Wang Hwei-Ming, Huang Yu-Wen, Huang Jen-Seng, Wang Cheng-Hsu, Kok Victor C, Hung Chao-Ming, Chen Han-Ming, Tzen Chin-Yuan
Division of Colorectal Surgery, Department of Surgery, Taichung Veterans General Hospital, No. 160, Sec. 3, Chungkang Road, Taichung, Taiwan.
Ann Surg Oncol. 2007 Oct;14(10):3011-8. doi: 10.1245/s10434-007-9503-8. Epub 2007 Jul 20.
Anaplastic thyroid carcinoma (ATC), a rare and highly malignant tumor, has long been thought to arise from well-differentiated carcinoma (WDC) such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC). The purpose of this study was to test this notion by examining whether and, if so, how often ATC harbors the oncogenes that are commonly associated with WDC, such as RAS in FTC and BRAF in PTC.
We analyzed the mutation hotspots of BRAF (codon 600) and N-, K-, and H-RAS (codons 12, 13, and 61) in 16 ATCs. We also examined two genes, PIK3CA (exons 9 and 20) and TP53 (exons 5-9), both of which have been reported in ATCs.
The results showed that approximately 31% (5 of 16) of ATCs harbored N-RAS mutation, 6% (1 of 16) had mutated BRAF, and approximately 56% (9 of 16) had mutated TP53. As to the three ATCs that had coexisted PTCs, mutated BRAF was detected in all PTC components but only in one ATC, while mutated PIK3CA was found in only one PTC component but not in the ATC.
A number of ATCs arise from WDCs, more often from RAS-mutant tumors than from BRAF-mutant tumors, implying that particular attention should be paid to the WDC harboring RAS mutation.
间变性甲状腺癌（ATC）是一种罕见的高恶性肿瘤，长期以来一直被认为起源于分化良好的癌（WDC），如滤泡状甲状腺癌（FTC）和乳头状甲状腺癌（PTC）。本研究的目的是通过检查ATC是否以及（如果是）多频繁地携带与WDC常见相关的癌基因，如FTC中的RAS和PTC中的BRAF，来验证这一观点。
我们分析了16例ATC中BRAF（密码子600）以及N -、K - 和H - RAS（密码子12、13和61）的突变热点。我们还检测了两个基因，PIK3CA（外显子9和20）和TP53（外显子5 - 9），这两个基因在ATC中均有报道。
结果显示，约31%（16例中的5例）的ATC携带N - RAS突变，6%（16例中的1例）有BRAF突变，约56%（16例中的9例）有TP53突变。对于3例同时存在PTC的ATC，在所有PTC成分中均检测到BRAF突变，但仅在1例ATC中检测到，而PIK3CA突变仅在1个PTC成分中发现，在ATC中未发现。
许多ATC起源于WDC，起源于RAS突变肿瘤的情况比起源于BRAF突变肿瘤的情况更常见，这意味着应特别关注携带RAS突变的WDC。
