HOMOZYGOUS DELETION, REARRANGEMENT AND HYPERMETHYLATION IMPLICATE CHROMOSOME REGION 3P14.3-3P21.3 IN SPORADIC BREAST-CANCER DEVELOPMENT
HOMOZYGOUS DELETION, REARRANGEMENT AND HYPERMETHYLATION IMPLICATE CHROMOSOME REGION 3P14.3-3P21.3 IN SPORADIC BREAST-CANCER DEVELOPMENT
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DOI：
10.1002/ijc.2910570406
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发表时间：
1994-05-15
影响因子：
6.4
通讯作者：
ETKIND, P
中科院分区：
文献类型：
--
作者：
BUCHHAGEN, DL;QIU, LP;ETKIND, P
对19例乳腺恶性肿瘤和2例乳腺良性纤维腺瘤3号染色体短臂上5个多态位点的杂合性进行了分析。使用定位于3pI4.3-3p2I.I的探针D3 S2鉴定了一个纯合缺失和一个重排。该探针还在6/18（33%）的恶性肿瘤样品中检测到2.0kb和/或3.4kb的新杂交片段，所述恶性肿瘤样品在用5 ′-甲基胞嘧啶不敏感酶Msp 1消化后与D3 S2探针杂交。Hpall和Mspl消化的比较显示，除了一个分析的肿瘤DNA之外，所有分析的肿瘤DNA都是高甲基化的。两种纤维腺瘤DNA甲基化程度不高，经Hpall消化后有3.4kb的杂交片段。这些恶性乳腺肿瘤DNA表现出3种机制，通过这些机制，假设位于3 pI 4 - 3 p2 I的肿瘤抑制基因可以失活：纯合缺失、重排和超甲基化，并强烈暗示该3 p染色体区域在乳腺肿瘤的发展中。(C)1994 Wiley-Liss，Inc.
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 3pI4.3-3p2I.I. 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 Mspl. Comparisons of Hpall and Mspl 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 Hpall digestion. These malignant breast-tumor DNAs exhibit 3 mechanisms by which a tumor-suppressor gene hypothesized to reside at 3pI4-3p2I could be inactivated: homozygous deletion, rearrangement and hypermethylation, and strongly implicate this 3p chromosome region in breast-tumor development. (C) 1994 Wiley-Liss, Inc.