Shin E, Fujita S, Takami K, Kurahashi H, Kurita Y, Kobayashi T, Mori T, Nishisho I, Takai S
Department of Medical Genetics, Osaka University Medical School, Suita.
Jpn J Cancer Res. 1993 Apr;84(4):402-8. doi: 10.1111/j.1349-7006.1993.tb00150.x.
To identify the localization of tumor suppressor genes, 22 pheochromocytomas (9 hereditary and 13 sporadic) were examined for loss of heterozygosity (LOH) on the short arm of chromosome 1 and on the long arm of chromosome 22 by using 11 polymorphic DNA markers on each chromosome arm. LOH on 1p was observed in 12 of 22 informative cases (55%) and on 22q in 8 of 20 informative cases (40%). There was no significant difference in the frequency of LOH on 1p or 22q between hereditary and sporadic cases. We could localize the commonly deleted regions as distal to D1S73 and proximal to D1S63 on 1p and distal to D22S24 and proximal to D22S1 on 22q. In addition, the relationship between LOH on 1p and 22q was studied in 20 pheochromocytomas which were informative for probes on both chromosome arms. Of eight tumors that showed LOH on 22q, allelic loss on 1p was also detected in seven. Thus, LOH on 22q was correlated significantly with LOH on 1p (P = 0.0249; Fisher's exact test). These results suggest that inactivation of multiple tumor suppressor genes may be required for development and progression of hereditary and non-hereditary pheochromocytoma.
为了确定肿瘤抑制基因的定位,利用每条染色体臂上的11个多态性DNA标记,对22例嗜铬细胞瘤(9例遗传性和13例散发性)进行了1号染色体短臂和22号染色体长臂杂合性缺失(LOH)检测。在22例信息充分的病例中,12例(55%)观察到1p上存在LOH,在20例信息充分的病例中,8例(40%)观察到22q上存在LOH。遗传性和散发性病例在1p或22q上的LOH频率无显著差异。我们可以将常见的缺失区域定位在1p上D1S73远端和D1S63近端以及22q上D22S24远端和D22S1近端。此外,在20例对两条染色体臂上的探针均有信息的嗜铬细胞瘤中研究了1p和22q上LOH之间的关系。在22q上显示LOH的8个肿瘤中,7个也检测到1p上等位基因缺失。因此,22q上的LOH与1p上的LOH显著相关(P = 0.0249;Fisher精确检验)。这些结果表明,遗传性和非遗传性嗜铬细胞瘤的发生和进展可能需要多个肿瘤抑制基因失活。