A recurrent chromosome breakpoint in breast cancer at the NRG1/Neuregulin 1/Heregulin gene
A recurrent chromosome breakpoint in breast cancer at the NRG1/Neuregulin 1/Heregulin gene
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DOI：
10.1158/0008-5472.can-04-1762
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发表时间：
2004-10-01
期刊：
影响因子：
11.2
通讯作者：
Edwards, PAW
中科院分区：
文献类型：
--
作者：
Huang, HE;Chin, SF;Edwards, PAW
大多数关于常见癌症基因组重排的研究都集中在区域性的获得和损失上，但有些重排可能会在特定基因内断裂。我们以前报道过，5个乳腺癌细胞系有染色体易位，NRG 1基因断裂，可能导致NRG 1表达异常。NRG 1编码Neuregulins I（以前称为Heregulins），ErbB/表皮生长因子受体家族成员的配体，包括ErbB 2/HER 2。我们现在已经在乳腺肿瘤的石蜡切片中筛选了NRG 1的断裂。通过荧光原位杂交筛选组织微阵列，杂交探针在预期断点的近端和远端。该筛选检测断裂，但不区分易位或缺失断裂点。在定制的8 p12高密度基因组阵列上用阵列比较基因组杂交验证筛选，以检测在断裂远端丢失的较低拷贝数的序列。我们还用不同的杂交探针精确地绘制了五个肿瘤中的断裂。在6%（19/323）的乳腺癌和一些肺癌和卵巢癌中检测到NRG 1断裂。在一项包含213例随访病例的未选择系列中，检测到断裂的乳腺癌往往为高级别（65%为III级，而阴性病例为284例）。它们与一般乳腺肿瘤一样，主要是ErbB 2低（13例中有11例低）和雌激素受体阳性（13例中有11例阳性）。
Most studies of genomic rearrangements in common cancers have focused on regional gains and losses, but some rearrangements may break within specific genes. We previously reported that five breast cancer cell lines have chromosome translocations that break in the NRG1 gene and that could cause abnormal NRG1 expression. NRG1 encodes the Neuregulins I (formerly the Heregulins), ligands for members of the ErbB/epidermal growth factor-receptor family, which includes ErbB2/HER2. We have now screened for breaks at NRG1 in paraffin sections of breast tumors. Tissue microarrays were screened by fluorescence in situ hybridization, with hybridization probes proximal and distal to the expected breakpoints. This screen detects breaks but does not distinguish between translocation or deletion breakpoints. The screen was validated with array-comparative genomic hybridization on a custom 8p12 high-density genomic array to detect a lower copy number of the sequences that were lost distal to the breaks. We also precisely mapped the breaks in five tumors with different hybridization probes. Breaks in NRG1 were detected in 6% (19 of 323) of breast cancers and in some lung and ovarian cancers. In an unselected series of 213 cases with follow-up, breast cancers where the break was detected tended to be high-grade (65% grade III compared with 284 of negative cases). They were, like breast tumors in general, mainly ErbB2 low (11 of 13 were low) and estrogen receptor positive (11 of 13 positive).