Miyaki M, Konishi M, Kikuchi-Yanoshita R, Enomoto M, Tanaka K, Takahashi H, Muraoka M, Mori T, Konishi F, Iwama T
Department of Biochemistry, Tokyo Metropolitan Institute of Medical Science, Japan.
Cancer Res. 1993 Nov 1;53(21):5079-82.
Desmoid tumors, which are locally invasive with recurrence but without metastasis, are frequently observed in patients with familial adenomatous polyposis after abdominal surgery or during pregnancy. This study analyzed mutation of the adenomatous polyposis coli gene in 8 desmoid tumors from 7 familial adenomatous polyposis patients using polymerase chain reaction-single-strand conformation polymorphism and the direct sequencing method. Seven somatic mutations, 1 somatic allele loss, and 6 germ-line mutations were detected. The majority of adenomatous polyposis coli gene mutations were deletions of 1 to 19 base pairs in exon 15, and all mutations led to the formation of stop codons. A somatic mutation with repetition of 82 base pairs from codon 1399 to 1426 was also observed in a desmoid, which was most likely caused by an error during replication or repair replication. No mutation was detected in exons 1 to 2 of H-ras, K-ras, and N-ras genes and in exons 5 to 8 of p53 gene, in these tumors. The simultaneous existence of somatic and germ-line alterations of adenomatous polyposis coli gene observed in all 8 tumors strongly suggests that inactivation of both alleles of adenomatous polyposis coli gene is involved in the development of desmoid tumors.
硬纤维瘤虽局部浸润且易复发但无转移，常见于家族性腺瘤性息肉病患者腹部手术后或孕期。本研究采用聚合酶链反应-单链构象多态性及直接测序法，分析了7例家族性腺瘤性息肉病患者的8个硬纤维瘤中腺瘤性息肉病（APC）基因的突变情况。共检测到7个体细胞突变、1个体细胞等位基因缺失和6个胚系突变。APC基因的大多数突变是第15外显子1至19个碱基对的缺失，所有突变均导致终止密码子的形成。在1个硬纤维瘤中还观察到1个从密码子1399至1426重复82个碱基对的体细胞突变，这很可能是复制或修复复制过程中的错误所致。在这些肿瘤中，H-ras、K-ras和N-ras基因的第1至2外显子以及p53基因的第5至8外显子均未检测到突变。在所有8个肿瘤中均观察到APC基因体细胞和胚系改变同时存在，这强烈提示APC基因两个等位基因的失活参与了硬纤维瘤的发生发展。
