High rate of BRAF and RET/PTC dual mutations associated with recurrent papillary thyroid carcinoma.
High rate of BRAF and RET/PTC dual mutations associated with recurrent papillary thyroid carcinoma.
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DOI：
10.1158/1078-0432.ccr-08-0933
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发表时间：
2009-01-15
期刊：
影响因子：
--
通讯作者：
Clayman GL
中科院分区：
文献类型：
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作者：
Henderson YC;Shellenberger TD;Williams MD;El-Naggar AK;Fredrick MJ;Cieply KM;Clayman GL
甲状腺乳头状癌（PTC）是最常见的甲状腺恶性肿瘤，通常具有 BRAF 突变或翻译重排（RET）/PTC 重排。 PTC通常具有BRAF突变或RET/PTC重排。复发性 PTC 患者的突变状态从未在大量人群中得到表征。在 54 名复发性 PTC 患者的队列中确定了突变状态，并分析了临床病理关系。通过 PCR 和基因组 DNA 测序确定 BRAF 和 ras 突变。通过逆转录-PCR 分析 RET/PTC 重排。 42/54 (77.8%) 复发性 PTC 患者中发现外显子 15 (V600E) BRAF 突变。 54 名患者中有 9 名 (16.7%) 检测到 RET/PTC 重排。此外，54 名复发性 PTC 患者中有 5 名 (9.3%) 同时具有 BRAF 突变和 RET/PTC 重排。在复发人群中发现的双重突变肿瘤的患病率远远超过历史上报道的原发性 PTC 患者的频率。具有双重突变的患者（80% 大于 45 岁）明显比仅具有 BRAF 突变的患者（38% 大于 45 岁）年龄更大。复发性 PTC 与主要 BRAF 突变显着相关。 RET/PTC 重排虽然通常与年轻患者的原发性 PTC 相关，但在复发性 PTC 患者中并不常见。此外，据其他人报道，复发性 PTC 患者的双重突变发生率高于原发性 PTC 患者。
Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, usually possesses BRAF mutation or rearranged in translation (RET)/PTC rearrangements. PTC usually possesses BRAF mutation or RET/PTC rearrangements. The mutation status of patients with recurrent PTC has never been characterized in a large population. Mutation status was determined in a cohort of 54 patients with recurrent PTC and analyzed for clinicopathologic relationships. BRAF and ras mutations were determined by PCR and sequencing of genomic DNA. RET/PTC rearrangements were analyzed by reverse transcription-PCR. BRAF mutation in exon 15 (V600E) was found in 42/54 (77.8%) recurrent PTC patients. The RET/PTC rearrangements were detected in 9 of 54 (16.7%) patients. In addition, 5 of 54 (9.3%) recurrent PTC patients had both a BRAF mutation and a RET/PTC rearrangement. The prevalence of tumors with dual mutations found in the recurrent population far exceeds the frequency historically reported for patients with primary PTC. Patients with dual mutations were significantly older (80% older than 45 years) than patients with a BRAF mutation alone (38% older than 45 years). Recurrent PTC is significantly associated with a predominant BRAF mutation. RET/PTC rearrangements, although commonly associated with primary PTCs in younger patients, are uncommonly found in recurrent PTC patients. In addition, the incidence of dual mutations was higher in patients with recurrent PTC than in those primary PTC, as reported by others.