Vuong Huy Gia, Kondo Tetsuo, Oishi Naoki, Nakazawa Tadao, Mochizuki Kunio, Inoue Tomohiro, Tahara Ippei, Kasai Kazunari, Hirokawa Mitsuyoshi, Tran Thong Minh, Katoh Ryohei
Department of Pathology, University of Yamanashi, Yamanashi, Japan.
Department of Pathology, Cho Ray Hospital, Ho Chi Minh, Vietnam.
Cancer Med. 2016 Aug;5(8):1883-9. doi: 10.1002/cam4.781. Epub 2016 Jun 5.
BRAF V600E mutation, RET rearrangements, and RAS mutations are the common genetic alterations in differentiated thyroid carcinomas derived from follicular thyroid cells. However, the relationship between these alterations and iodine intake is still controversial. To clarify the influence of iodine intake on the occurrence of differentiated thyroid carcinomas, we performed molecular analyses for two differentiated carcinomas, papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs), from an iodine-rich country (Japan) and an iodine-deficient country (Vietnam). We examined 120 PTCs (67 Japanese and 53 Vietnamese) and 74 FTCs (51 Japanese and 23 Vietnamese). We carried out allele-specific polymerase chain reaction (AS-PCR) for BRAF V600E, PCR and direct sequencing for RAS mutations (codon 12, 13, and 61 in NRAS, HRAS, and KRAS), and RT-PCR for RET/PTC1 and RET/PTC3. BRAF V600E was present in 55/67 (82.1%) Japanese PTCs and 44/53 (83%) Vietnamese PTCs. RET/PTC1 was identified in only one PTC from each country, and no samples had RET/PTC3. NRAS mutation was found in 17/51 (33.3%) Japanese FTCs and 4/23 (17.4%) Vietnamese FTCs. NRAS mutation was cited in codon 61 (20 cases) and codon 12 (one case). None of FTCs had KRAS or HRAS mutations. There were no significant differences in the prevalence of BRAF V600E, RET/PTC, or RAS mutations between the two countries. Our study showed no differences in genetic alterations of thyroid cancers from iodine-rich and iodine-deficient countries, possibly suggesting that iodine intake might not affect the genetic alterations of differentiated thyroid cancer.
BRAF V600E突变、RET重排和RAS突变是源自滤泡状甲状腺细胞的分化型甲状腺癌中常见的基因改变。然而，这些改变与碘摄入之间的关系仍存在争议。为了阐明碘摄入对分化型甲状腺癌发生的影响，我们对来自富碘国家（日本）和缺碘国家（越南）的两种分化型癌——乳头状甲状腺癌（PTC）和滤泡状甲状腺癌（FTC）进行了分子分析。我们检测了120例PTC（67例日本患者和53例越南患者）和74例FTC（51例日本患者和23例越南患者）。我们对BRAF V600E进行了等位基因特异性聚合酶链反应（AS-PCR），对RAS突变（NRAS、HRAS和KRAS中的密码子12、13和61）进行了PCR和直接测序，对RET/PTC1和RET/PTC3进行了逆转录PCR（RT-PCR）。BRAF V600E在55/67（82.1%）的日本PTC和44/53（83%）的越南PTC中存在。每个国家仅在1例PTC中鉴定出RET/PTC1，且无样本检测到RET/PTC3。NRAS突变在17/51（33.3%）的日本FTC和4/23（17.4%）的越南FTC中被发现。NRAS突变见于密码子61（20例）和密码子12（1例）。所有FTC均未检测到KRAS或HRAS突变。两国之间BRAF V600E、RET/PTC或RAS突变的发生率无显著差异。我们的研究表明，富碘和缺碘国家甲状腺癌的基因改变没有差异，这可能表明碘摄入可能不会影响分化型甲状腺癌的基因改变。
