Bièche I, Champème M H, Lidereau R
Laboratoire d'Oncogénétique, Centre René Huguenin, St. Cloud, France.
Cancer Res. 1994 Aug 15;54(16):4274-6.
To investigate the possibility of collaboration between telomeric deletion on the short arm of chromosome 1 and genetic amplification similar to that described in human neuroblastoma, 122 human primary breast tumors were examined by restriction fragment length polymorphism analysis for loss of heterozygosity on 1p32-pter and for the three most frequently amplified genetic regions in breast carcinomas (MYC and ERBB2 protooncogenes and the chromosomal region 11q13). Allelic losses at one or more loci on the telomeric part of the short arm of chromosome 1 was observed in 57 (47%) of 122 informative tumors. MYC, ERBB2, and the 11q13 region were amplified in 23, 20, and 21% of breast tumors, respectively. A correlation was found between loss of heterozygosity on chromosome 1p32-pter and amplification of the MYC (formerly c-myc) protooncogene (P = 0.003), suggesting that these two genetic events may collaborate during tumor progression in human breast cancer. These results, together with those obtained in human neuroblastoma, suggest that the distal part of the short arm of chromosome 1 harbors an unidentified tumor suppressor gene(s), whose inactivation may be involved in MYC family gene amplification (an example of genetic instability) in tumors of various cellular origins.
为了研究1号染色体短臂上的端粒缺失与类似于人类神经母细胞瘤中所描述的基因扩增之间存在协作的可能性，我们通过限制性片段长度多态性分析，对122例人原发性乳腺癌进行检测，以确定1p32 - pter区域的杂合性缺失情况以及乳腺癌中三个最常发生扩增的基因区域（MYC和ERBB2原癌基因以及染色体区域11q13）。在122例信息充分的肿瘤中，有57例（47%）在1号染色体短臂端粒部分的一个或多个位点观察到等位基因缺失。MYC、ERBB2和11q13区域分别在23%、%和21%的乳腺肿瘤中发生扩增。在1p32 - pter染色体上的杂合性缺失与MYC（原c - myc）原癌基因的扩增之间发现存在相关性（P = 0.003），这表明这两个基因事件可能在人类乳腺癌的肿瘤进展过程中相互协作。这些结果，连同在人类神经母细胞瘤中获得的结果，表明1号染色体短臂的远端区域存在一个未被鉴定的肿瘤抑制基因，其失活可能参与了各种细胞起源肿瘤中MYC家族基因扩增（基因不稳定的一个例子）。
