Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R, Meltzer P, Gusterson B, Esteller M, Kallioniemi O P, Wilfond B, Borg A, Trent J, Raffeld M, Yakhini Z, Ben-Dor A, Dougherty E, Kononen J, Bubendorf L, Fehrle W, Pittaluga S, Gruvberger S, Loman N, Johannsson O, Olsson H, Sauter G
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4470, USA.
N Engl J Med. 2001 Feb 22;344(8):539-48. doi: 10.1056/NEJM200102223440801.
Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that the genes expressed by these two types of tumors are also distinctive, perhaps allowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles.
RNA from samples of primary tumor from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype.
Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed significantly from each other. An analysis of variance between the levels of gene expression and the genotype of the samples identified 176 genes that were differentially expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differences between breast tumors with BRCA1 mutations and those with BRCA2 mutations.
Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression profile of the cancer.
许多遗传性乳腺癌病例是由BRCA1或BRCA2基因的突变引起的。这些癌症的组织病理学变化通常是突变基因的特征。我们推测这两种类型肿瘤所表达的基因也具有独特性，或许能让我们根据基因表达谱来识别遗传性乳腺癌病例。
将来自7名BRCA1突变携带者、7名BRCA2突变携带者以及7名散发性乳腺癌患者的原发性肿瘤样本的RNA，与包含5361个基因的6512个互补DNA克隆的微阵列进行比较。采用统计分析来确定一组能够区分BRCA1基因型和BRCA2基因型的基因。
多变量分类函数的排列分析表明，携带BRCA1突变的肿瘤、携带BRCA2突变的肿瘤以及散发性肿瘤的基因表达谱彼此之间存在显著差异。对基因表达水平与样本基因型之间的方差分析确定了176个在携带BRCA1突变的肿瘤和携带BRCA2突变的肿瘤中差异表达的基因。鉴于该组中某些基因的已知特性，我们的研究结果表明携带BRCA1突变的乳腺肿瘤与携带BRCA2突变的乳腺肿瘤之间存在功能差异。
携带BRCA1突变的乳腺癌和携带BRCA2突变的乳腺癌表达的基因组存在显著差异。我们的结果表明，遗传性突变会影响癌症的基因表达谱。
