RAS ONCOGENE MUTATIONS IN BENIGN AND MALIGNANT THYROID NEOPLASMS
RAS ONCOGENE MUTATIONS IN BENIGN AND MALIGNANT THYROID NEOPLASMS
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DOI：
10.1210/jcem-73-4-832
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发表时间：
1991-10-01
影响因子：
5.8
通讯作者：
JAMESON, JL
中科院分区：
文献类型：
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作者：
KARGA, H;LEE, JK;JAMESON, JL
目前的肿瘤发生模型提出，在从正常细胞到恶性表型的进展过程中发生了一系列遗传改变。三种ras基因（K-ras、H-ras和N-ras）的突变已在许多人类肿瘤（包括甲状腺癌）中被鉴定。在这项研究中，我们检查了良性和恶性甲状腺肿瘤的基因组DNA中已知可激活ras癌基因（密码子12、13和61）的突变。通过聚合酶链反应扩增来自冷冻手术切除组织（n = 8）和来自福尔马林固定的石蜡包埋组织（n = 30）的DNA，并使用寡核苷酸特异性杂交筛选突变。在滤泡性腺瘤中未发现突变（n = 9）。在滤泡状癌中，14例肿瘤中有2例含有突变（N-ras 61，Gln至Arg），并且这两例患者都有骨转移。15例乳头状癌中有1例ras基因突变（H-ras 12，Gly → Ser）。与其他研究相比，我们发现ras基因突变在良性和恶性甲状腺肿瘤中相对少见。需要对大量肿瘤进行研究，并对不同患者人群进行比较，以评估N-ras 61突变与临床侵袭性滤泡癌的可能相关性。
Current models for tumorigenesis propose that a series of genetic alterations occur during the progression from the normal cell to the malignant phenotype. Mutations in each of the three ras genes (K-ras, H-ras, and N-ras) have been identified in many human neoplasms, including thyroid cancer. In this study we examined genomic DNA from benign and malignant thyroid neoplasms for mutations that are known to activate the ras oncogenes (codons 12, 13, and 61). DNA from frozen surgically excised tissue (n = 8) and from formalin-fixed paraffin-embedded tissue (n = 30) was amplified by the polymerase chain reaction and screened for mutations using oligonucleotide-specific hybridization. No mutations were identified in follicular adenomas (n = 9). In follicular carcinomas, 2 of 14 tumors contained mutations (N-ras 61, Gln to Arg), and both of these patients had bone metastases. One of 15 papillary carcinomas had a ras mutation (H-ras 12, Gly to Ser). In contrast to other studies, we found that ras mutations are relatively uncommon in both benign and malignant thyroid neoplasms. Studies of larger numbers of tumors and comparisons of different patient populations will be required to assess a possible association of mutations in N-ras 61 with clinically aggressive follicular cancer.