Watanabe M, Shiraishi T, Yatani R, Nomura A M, Stemmermann G N
Department of Pathology, Mie University School of Medicine, Tsu, Japan.
Int J Cancer. 1994 Jul 15;58(2):174-8. doi: 10.1002/ijc.2910580205.
Latent carcinomas of the prostate, discovered at autopsy in men with no prior treatment for prostatic disease, were studied for ras proto-oncogene mutations. Subjects included 21 Japanese, 15 U.S. whites, 15 U.S. blacks, 20 Hawaiian Japanese and 10 Colombians. PCR and sequence-specific oligonucleotide hybridization identified mutations in 5 Japanese, in 1 Hawaiian Japanese, in 1 U.S. black, in 1 U.S. white and in 3 Colombians. The 5 Japanese tumor samples contained 3 point mutations in codon 12 of K-ras and 2 mutations in codon 12 of N-ras respectively. One tumor in a Hawaiian Japanese man also showed a K-ras point mutation at codon 12. Two Colombians and one U.S. black man had tumors with mutations at codon 61 of H-ras, while 1 Colombian showed an N-ras mutation at this codon. The overall frequency of ras gene mutations was low, but point mutations in codon 12 were most common in latent tumors of Japanese, who experienced the lowest incidence and mortality from this tumor. Latent tumors in men from ethnic groups with high mortality and incidence rates showed fewer ras mutations than the Japanese, and these were more likely to involve codon 61. This finding is consistent with prior studies of more aggressive clinical cancers in Japanese men that indicated a higher frequency of mutations at codon 61.
对在尸检中发现的、生前未接受过前列腺疾病治疗的前列腺潜伏癌患者进行了原癌基因ras突变研究。研究对象包括21名日本人、15名美国白人、15名美国黑人、20名夏威夷日本人以及10名哥伦比亚人。通过聚合酶链反应（PCR）和序列特异性寡核苷酸杂交技术，在5名日本人、1名夏威夷日本人、1名美国黑人、1名美国白人以及3名哥伦比亚人的样本中检测到了ras基因突变。这5名日本人的肿瘤样本中，分别在K-ras基因的第12密码子处有3个点突变，在N-ras基因的第12密码子处有2个突变。1名夏威夷日本男性的肿瘤样本在K-ras基因的第12密码子处也出现了一个点突变。2名哥伦比亚人和1名美国黑人的肿瘤样本在H-ras基因的第61密码子处发生了突变，而1名哥伦比亚人的肿瘤样本在该密码子处出现了N-ras基因突变。ras基因突变的总体频率较低，但在日本潜伏癌患者中，第12密码子处的点突变最为常见，而日本人患这种癌症的发病率和死亡率也是最低的。与日本人相比，高死亡率和高发病率种族男性的潜伏癌ras基因突变较少，且这些突变更可能发生在第61密码子处。这一发现与之前对日本男性侵袭性更强的临床癌症研究结果一致，即第61密码子处的突变频率更高。
