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寡核苷酸微阵列-CGH 可识别蕈样肉芽肿肿瘤分期的基因组亚群和预后标志物。

Oligonucleotide array-CGH identifies genomic subgroups and prognostic markers for tumor stage mycosis fungoides.

机构信息

Laboratori de Citogènetica Molecular, Servei de Patologia, IMIM-Hospital del Mar, Barcelona, Spain.

出版信息

J Invest Dermatol. 2010 Apr;130(4):1126-35. doi: 10.1038/jid.2009.306. Epub 2009 Sep 17.

DOI:10.1038/jid.2009.306
PMID:19759554
Abstract

Mycosis fungoide (MF) patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present European Organization for Research and Treatment of Cancer (EORTC) multicenter study, the genomic profile of 41 skin biopsies from tumor stage MF (MFt) was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter, and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2, and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21, and 10q26qter, were defined as prognostic markers showing a significant correlation with overall survival (OS) (P=0.042, 0.017, and 0.022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (>5 DNA aberrations), showing that the genomic unstable group had a shorter OS (P=0.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B, and MTAP) and 10q26qter (MGMT and EBF3) may have an important role in prognosis. In addition, we describe the MFt genomic instability profile, which, to our knowledge, has not been reported earlier.

摘要

蕈样肉芽肿(MF)患者若出现肿瘤或皮肤外侵犯,通常预后不良,目前尚无治愈疗法。在目前的欧洲癌症研究与治疗组织(EORTC)多中心研究中,使用高分辨率寡核苷酸阵列比较基因组杂交平台分析了 41 例肿瘤期 MF(MFt)皮肤活检的基因组谱。76%的病例显示基因组异常。最常见的不平衡是 7q33.3q35 的增益,其次是 17q21.1、8q24.21、9q34qter 和 10p14,以及 9p21.3 的缺失,其次是 9q31.2、17p13.1、13q14.11、6q21.3、10p11.22、16q23.2 和 16q24.3。三个特定的染色体区域,9p21.3、8q24.21 和 10q26qter,被定义为预后标志物,与总生存(OS)显著相关(P=0.042、0.017 和 0.022)。此外,我们还建立了两个 MFt 基因组亚组,区分稳定组(0-5 个 DNA 异常)和不稳定组(>5 个 DNA 异常),结果表明基因组不稳定组的 OS 更短(P=0.05)。因此,我们得出结论,特定的染色体异常,如 8q24.21(MYC)的增益和 9p21.3(CDKN2A、CDKN2B 和 MTAP)和 10q26qter(MGMT 和 EBF3)的缺失,可能在预后中具有重要作用。此外,我们描述了 MFt 的基因组不稳定性谱,据我们所知,这在以前的报告中尚未报道。

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Oligonucleotide array-CGH identifies genomic subgroups and prognostic markers for tumor stage mycosis fungoides.寡核苷酸微阵列-CGH 可识别蕈样肉芽肿肿瘤分期的基因组亚群和预后标志物。
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