Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis.
Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis.
复制标题
1p36 缺失是肠道肿瘤发生中的主要染色体畸变。
作者：
G. Bardi;N. Pandis;C. Fenger;O. Kronborg;L. Bomme;S. Heim
对良性肠道肿瘤短期培养物的细胞遗传学分析显示，5 个结直肠腺瘤、1 个乳头腺瘤和 1 个直肠增生性息肉存在克隆染色体畸变。一种腺瘤仅存在数值畸变，但在所有其他肿瘤中都发现了结构重排，导致 1p 遗传物质丢失。在其中三个案例中，删除仅限于 1p36 带；其余的则丢失了较大的 1p 片段。 1 号染色体重排是三种腺瘤（均伴有轻度或中度不典型增生）和增生性息肉中唯一的核型异常。两种在 1p 缺失之外还有额外畸变的腺瘤均显示出严重的发育不良。我们得出的结论是，细胞遗传学上可检测到的 1p36 遗传信息丢失是肠道肿瘤发生中的早期、看似主要的癌前事件。以 1p- 为唯一变化的腺瘤仅表现出轻度或中度不典型增生，并且在增生性息肉中也发现了 del(1p)，这一事实表明，这种畸变更多地与诱导过度增殖有关，而不是与肠粘膜的分化紊乱有关。
Cytogenetic analysis of short-term cultures from benign intestinal tumors revealed clonal chromosome aberrations in five colorectal adenomas, one adenoma of the papilla Vateri, and one hyperplastic polyp of the rectum. One adenoma had numerical aberrations only, but in all other tumors structural rearrangements were found that led to loss of genetic material from 1p. In three of the cases, the deletion was restricted to the 1p36 band; the rest had lost larger 1p segments. The rearrangement of chromosome 1 was the sole karyotypic anomaly in three adenomas, all with mild or moderate dysplasia, and in the hyperplastic polyp. Both adenomas that had additional aberrations beyond the 1p loss showed severe dysplasia. We conclude that cytogenetically detectable loss of genetic information from 1p36 is an early, seemingly primary, premalignant event in intestinal tumorigenesis. The fact that the adenomas with 1p- as the sole change showed only mild or moderate dysplasia and that the del(1p) was found also in the hyperplastic polyp suggests that this aberration is more related to the induction of hyperproliferation than to differentiation disturbances in the intestinal mucosa.