Zhai Y L, Nikaido T, Orii A, Horiuchi A, Toki T, Fujii S
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan.
Gynecol Oncol. 1999 Dec;75(3):453-9. doi: 10.1006/gyno.1999.5629.
Leiomyosarcoma of the uterus is a rare smooth muscle tumor; it is extremely malignant and the rates of local recurrence and metastasis are high. Since tumor suppressor genes are commonly altered in malignant tumors, it is possible that mutations in such genes are involved in the development of uterine leiomyosarcoma.
Fifty-five patients (37-70 years of age) diagnosed as having smooth muscle tumors of the uterus were selected. DNA was extracted from four or five 8-microm-thick consecutive tissue sections of each smooth muscle tumor from the paraffin-embedded blocks. Loss of heterozygosity (LOH) was investigated at nine loci within or close to tumor suppressor genes (TP53, RB1, DCC, NM23, WT1, D14S267, P16, DPC4, PTCH).
Nineteen of twenty leiomyosarcomas revealed at least one instance of LOH among eight of the nine markers tested (one locus showed no LOH at all). In fact, 11 of the 20 cases exhibited two or more instances of LOH and, of the remaining 9 cases, 4 showed a point mutation of p53 in addition to an alteration in one of the 9 markers, while one exhibited a p53 mutation only.
An accumulation of genetic alterations among tumor suppressor genes may play a key role in the tumorigenesis and progression of uterine leiomyosarcoma.
子宫平滑肌肉瘤是一种罕见的平滑肌肿瘤；其恶性程度极高，局部复发和转移率也很高。由于肿瘤抑制基因在恶性肿瘤中通常会发生改变，因此这些基因的突变可能参与了子宫平滑肌肉瘤的发生发展。
选取55例诊断为子宫平滑肌肿瘤的患者（年龄37 - 70岁）。从石蜡包埋块中每个平滑肌肿瘤的4或5个连续的8微米厚组织切片中提取DNA。研究肿瘤抑制基因（TP53、RB1、DCC、NM23、WT1、D14S267、P16、DPC4、PTCH）内部或附近9个位点的杂合性缺失（LOH）情况。
20例平滑肌肉瘤中有19例在检测的9个标记中的8个标记中至少出现1例LOH（1个位点未出现任何LOH）。实际上，20例中有11例出现2次或更多次LOH，其余9例中，4例除9个标记之一发生改变外还出现p53点突变，1例仅出现p53突变。
肿瘤抑制基因间遗传改变的积累可能在子宫平滑肌肉瘤的肿瘤发生和进展中起关键作用。
