Buchhagen D L, Qiu L, Etkind P
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Int J Cancer. 1994 May 15;57(4):473-9. doi: 10.1002/ijc.2910570406.
DNAs from 19 malignant human breast tumors and 2 benign fibroadenomas were analyzed for heterozygosity at 5 polymorphic loci on the short arm of chromosome 3. One homozygous deletion and one rearrangement were identified using probe D3S2 which maps to 3p14.3-3p21.1. This probe also detected novel hybridizing fragments of 2.0 kb and/or 3.4 kb in 6/18 (33%) of the malignant tumor samples that hybridized with the D3S2 probe following digestion with the 5'-methylcytosine-insensitive enzyme MspI. Comparisons of HpaII and MspI digestion showed that all but one of the tumor DNAs analyzed were hypermethylated. The two fibroadenoma DNAs were not as highly methylated and had hybridizing fragments of 3.4 kb after HpaII digestion. These malignant breast-tumor DNAs exhibit 3 mechanisms by which a tumor-suppressor gene hypothesized to reside at 3p14-3p21 could be inactivated: homozygous deletion, rearrangement and hypermethylation, and strongly implicate this 3p chromosome region in breast-tumor development.
对来自19例恶性人乳腺肿瘤和2例良性纤维腺瘤的DNA，分析了位于3号染色体短臂上5个多态位点的杂合性。使用定位在3p14.3 - 3p21.1的探针D3S2鉴定出1个纯合缺失和1个重排。在用对5'-甲基胞嘧啶不敏感的酶MspI消化后，该探针还在与D3S2探针杂交的18例恶性肿瘤样本中的6例（33%）中检测到2.0 kb和/或3.4 kb的新杂交片段。对HpaII和MspI消化的比较表明，除1例分析的肿瘤DNA外，其余均为高甲基化。两个纤维腺瘤DNA甲基化程度不高，HpaII消化后有3.4 kb的杂交片段。这些恶性乳腺肿瘤DNA表现出3种机制，据此推测位于3p14 - 3p21的肿瘤抑制基因可能失活：纯合缺失、重排和高甲基化，并有力地表明3号染色体这个区域与乳腺肿瘤的发生有关。
