Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer.
Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer.
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发表时间：
1995-10
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通讯作者：
J. Isola;O. Kallioniemi;L. Chu;S. Fuqua;S. Hilsenbeck;C. Osborne;F. Waldman
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作者：
J. Isola;O. Kallioniemi;L. Chu;S. Fuqua;S. Hilsenbeck;C. Osborne;F. Waldman
乳腺癌的进展是由多种遗传畸变的复杂模式决定的，其与患者预后的关系尚不清楚。在这项研究中，我们进行了全基因组筛查，以检测与淋巴结阴性乳腺癌临床结局相关的遗传变化。比较基因组杂交用于筛选23例淋巴结阴性乳腺癌患者（随访至少5年后无疾病复发）和25例淋巴结阴性乳腺癌患者（随访前5年期间复发）所有人类染色体的DNA序列增益和损失。每个肿瘤的遗传畸变总数（拷贝数增加和丢失）在复发组（P = 0.019）和死于乳腺癌的患者亚组（P = 0.0022）中显著更高。当分别分析拷贝数损失和增加时，只有损失是显著的（复发率P = 0.013，总生存率P = 0.002）。在所涉及的单个位点中，8号染色体长臂的高水平增益与复发显著相关（P = 0.01，Fisher精确检验）。7例（15%）患者染色体20 q12 -13 DNA序列扩增，其中6例在确诊后32个月内早期复发。通过比较基因组杂交进行的全基因组综述表明，遗传畸变总数较高的遗传晚期淋巴结阴性乳腺癌可能预后不良，并且两个特定区域8 q和20 q13的拷贝数增加可能赋予更具侵袭性的表型。这项初步研究的结果表明，DNA序列拷贝数畸变的总数的测定可能有助于治疗决策。应开发特异性探针，以检测大量患者中8 q和20 q12 -13扩增的预后价值。
Breast cancer progression is determined by a complex pattern of multiple genetic aberrations the association of which with patient prognosis is unknown. In this study, we have undertaken a genome-wide screening to detect genetic changes associated with clinical outcome in node-negative breast cancer. Comparative genomic hybridization was used to screen for DNA sequence gains and losses across all human chromosomes in 23 tumors from node-negative breast cancer patients with no disease recurrence after at least 5 years of follow-up and in 25 node-negative patients with recurrence during the first 5 years of follow-up. The total number of genetic aberrations (copy number gains and losses) per tumor was significantly greater in the recurrence group (P = 0.019) and in the subgroup of these patients who died as a result of breast cancer (P = 0.0022). When copy number losses and gains were analyzed separately, only losses were significant (P = 0.013 for recurrence and P = 0.002 for overall survival). Of the individual loci involved, a high level gain of the long arm of chromosome 8 was significantly associated with recurrence (P = 0.01, Fisher's exact test). Furthermore, amplification of DNA sequences at chromosome 20q12-13 was found in 7 cases (15%), 6 of which had early recurrence within 32 months of diagnosis. This genome-wide overview by comparative genomic hybridization suggests that genetically advanced node-negative breast cancers having a high overall number of genetic aberrations may have a poor prognosis and that increased copy number of two specific regions, 8q and 20q13, may confer a more aggressive phenotype. Results of this pilot study suggest that determination of the total number of DNA sequence copy number aberrations may help therapeutic decision making. Specific probes should be developed to test the prognostic value of 8q and 20q12-13 amplifications in large numbers of patients.