Genomic loss of 18p predicts an adverse clinical outcome in patients with high-risk breast cancer.
Genomic loss of 18p predicts an adverse clinical outcome in patients with high-risk breast cancer.
复制标题
18p 基因组缺失预示着高危乳腺癌患者会出现不良临床结果。
作者：
J. Climent;J. Martinez;D. Blesa;M. Garcia;R. Sáez;D. Sánchez;P. Azagra;A. Lluch;J. Garcia
采用比较基因组杂交方法，研究了34例淋巴结阳性高危乳腺癌(HRBC)患者的基因组失衡对临床预后的影响。所有患者均接受大剂量化疗和自体干细胞移植。平均每个肿瘤的染色体不平衡数为11(范围2-24)，包括1q(59%)、17q(38%)、8q和16p(分别为35%)、20q(32%)和19p(26%)上的DNA过度表达，以及9p和18q(41%)、8p、11q和18p(38%)、17p(32%)、4p和Xq(29%)和16q(26%)的基因组丢失。基因组改变与临床病理特征之间最显著的关联是8P缺失与孕激素受体阳性的相关性(P<；0.005)。中位随访时间为74个月，15名患者(44%)复发。单因素分析显示，HER-2/neu基因座扩增/扩增17q的患者无病生存期较长(P=0.02)，而18p基因缺失的患者复发概率较高(P=0.003)。在多因素分析中，丢失18P是唯一与较短无病生存期相关的参数(相对危险度4.895%可信区间1.57-14.8；P=0.006)。综上所述，我们的数据表明，肿瘤基因组图谱可能是预测HRBC临床结果的有价值的标记物。此外，18P基因缺失可能是HRBC患者中预后较差的亚群。
The impact of the genomic imbalances on the clinical outcome of 34 patients with lymph-node positive high-risk breast cancer (HRBC) was investigated using comparative genomic hybridization. All of the patients were uniformly treated with high-dose chemotherapy and autologous stem cell transplantation. The average number of chromosomal imbalances per tumor was 11 (range, 2-24), including DNA overrepresentation on chromosomes 1q (59%), 17q (38%), 8q and 16p (35% each), 20q (32%), and 19p (26%), and genomic losses involving 9p and 18q (41%), 8p, 11q, and 18p (38%), 17p (32%), 4p and Xq (29%), and 16q (26%). The most significant association among genomic changes and clinical-pathological features was the correlation of the loss of 8p with progesterone receptor positivity (P < 0.005). With a median follow-up time of 74 months, 15 patients (44%) have relapsed. In the univariate analysis, patients with gain/amplification of 17q including the HER-2/neu gene locus had a longer disease-free survival (P = 0.02), whereas those with genomic loss of 18p had a higher probability of relapse (P = 0.003). In multivariate analysis, the loss of 18p was the only parameter correlated with shorter disease-free survival (relative risk, 4.8; 95% confidence interval, 1.57-14.8; P = 0.006). In summary, our data indicate that the tumoral genomic profile may represent a valuable marker for predicting the clinical outcome in HRBC. Furthermore, the genomic loss of 18p may identify a poor prognostic subgroup of patients with HRBC.
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DOI：
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发表时间：
1995-10
期刊：
The American journal of pathology
影响因子：
--
作者：
J. Isola;O. Kallioniemi;L. Chu;S. Fuqua;S. Hilsenbeck;C. Osborne;F. Waldman
通讯作者：
J. Isola;O. Kallioniemi;L. Chu;S. Fuqua;S. Hilsenbeck;C. Osborne;F. Waldman
DOI：
--
发表时间：
1999-12
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
J. Isola;L. Chu;S. Devries;K. Matsumura;K. Chew;B. Ljung;F. Waldman
通讯作者：
J. Isola;L. Chu;S. Devries;K. Matsumura;K. Chew;B. Ljung;F. Waldman
影响因子：
158.5
作者：
MUSS, HB;THOR, AD;HENDERSON, IC
通讯作者：
HENDERSON, IC
DOI：
10.1073/pnas.91.6.2156
发表时间：
1994-03-15
影响因子：
11.1
作者：
KALLIONIEMI, A;KALLIONIEMI, OP;WALDMAN, FM
通讯作者：
WALDMAN, FM
影响因子：
10.3
作者：
Paik, SM;Bryant, J;Wolmark, N
通讯作者：
Wolmark, N