Drabkin H, Kao F T, Hartz J, Hart I, Gazdar A, Weinberger C, Evans R, Gerber M
Eleanor Roosevelt Institute for Cancer Research, Denver, CO 80206.
Proc Natl Acad Sci U S A. 1988 Dec;85(23):9258-62. doi: 10.1073/pnas.85.23.9258.
Human genes homologous to the v-erbA oncogene of avian erythroblastosis virus have been mapped to at least two human chromosomes. Recently, the ERBA2 gene was shown to encode a thyroid hormone receptor and localized to chromosome 3 by using flow-sorted chromosomes. We now demonstrate that this gene is located at 3p22----3p24.1, using both somatic cell hybrids and in situ hybridization studies. Since this localization is close to the distal border of the small cell lung cancer (SCLC) 3p14----3p23 deletion, we undertook additional studies to examine the ERBA2 gene in SCLC. Using somatic cell hybrids constructed from the SCLC line NCI-H182 as well as matched patient tumor and control tissue samples, we found that ERBA2 is variably deleted. Therefore, ERBA2 defines at the molecular level the distal border of the SCLC deletion and further implies that the putative suppressor gene is located centromeric of this locus. We also determined that, at least in NCI-H182, the 3p14 breakpoint is proximal to the constitutive 3p14.2 fragile site. These studies would indicate that the mechanism or initiation site of chromosomal rearrangement in SCLC is different from that which occurs during induction of the 3p14 fragile site by aphidicolin.
与禽成红细胞增多症病毒的v-erbA癌基因同源的人类基因已被定位到至少两条人类染色体上。最近，ERBA2基因被证明编码一种甲状腺激素受体，并通过使用流式细胞分选的染色体将其定位到3号染色体上。我们现在通过体细胞杂交和原位杂交研究证明，该基因位于3p22----3p24.1。由于这一定位靠近小细胞肺癌（SCLC）3p14----3p23缺失的远端边界，我们进行了额外的研究以检测SCLC中的ERBA2基因。使用从小细胞肺癌细胞系NCI-H182构建的体细胞杂交体以及匹配的患者肿瘤和对照组织样本，我们发现ERBA2存在不同程度的缺失。因此，ERBA2在分子水平上定义了小细胞肺癌缺失的远端边界，并进一步表明假定的抑癌基因位于该位点的着丝粒侧。我们还确定，至少在NCI-H182中，3p14断点位于组成型3p14.2脆性位点的近端。这些研究表明，小细胞肺癌中染色体重排的机制或起始位点与阿非科林诱导3p14脆性位点时发生的情况不同。
