Miyauchi A, Futami H, Hai N, Yokozawa T, Kuma K, Aoki N, Kosugi S, Sugano K, Yamaguchi K
Kuma Hospital, Kobe.
Jpn J Cancer Res. 1999 Jan;90(1):1-5. doi: 10.1111/j.1349-7006.1999.tb00658.x.
Multiple endocrine neoplasia (MEN) type 2B is a clinically distinct entity among the autosomal dominant MEN 2 syndromes. Most patients with MEN 2B carry a germline mutation (M918T) of the RET proto-oncogene, while a few carry A883F. We examined a patient with MEN 2B, but without M918T or A883F, and her relatives. Here, we report the presence in this patient of 2 germline mutations, V804M and Y806C in the same allele. While the novel Y806C was inherited from her father, its carriers (her father and brother) was not affected by MEN 2. In contrast, V804M was a de novo mutation, that has been reported in patients with familial medullary thyroid carcinoma. Combinations of mutations of the RET proto-oncogene may cause oncogenic activities different from those of single mutations.
多发性内分泌腺瘤病（MEN）2B型是常染色体显性遗传的MEN 2综合征中的一种临床独特类型。大多数MEN 2B患者携带RET原癌基因的种系突变（M918T），少数携带A883F。我们检查了一名患有MEN 2B但无M918T或A883F的患者及其亲属。在此，我们报告该患者同一等位基因中存在2种种系突变，V804M和Y806C。虽然新发现的Y806C是从她父亲遗传而来，但其携带者（她的父亲和兄弟）未受MEN 2影响。相比之下，V804M是一种新发突变，曾在家族性甲状腺髓样癌患者中报道过。RET原癌基因突变的组合可能导致与单个突变不同的致癌活性。
