Copy number analysis of ductal carcinoma in situ with and without recurrence.
复发性及非复发性导管原位癌拷贝数目分析
Gorringe KL,Hunter SM,Pang JM,Opeskin K,Hill P,Rowley SM,Choong DY,Thompson ER,Dobrovic A,Fox SB,Mann GB,Campbell IG
Abstract
Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer and a frequent mammographic finding requiring treatment. Up to 25% of DCIS can recur and half of recurrences are invasive, but there are no reliable biomarkers for recurrence. We hypothesised that copy number aberrations could predict likelihood of recurrence. We analysed a cohort of pure DCIS cases treated only with wide local excision for genome-wide copy number and loss of heterozygosity using Affymetrix OncoScan MIP arrays. Cases included those without recurrence within 7 years (n=25) and with recurrence between 1 and 5 years after diagnosis (n=15). Pure DCIS were broadly similar in copy number changes compared with invasive breast cancer, with the consistent exception of a greater frequency of ERBB2 amplification in DCIS. There were no significant differences in age or ER status between the cases with a recurrence vs those without. Overall, the DCIS cases with recurrence had more copy number events than the DCIS without recurrence. The increased copy number appeared non-random with several genomic regions showing an increase in frequency in recurrent cases, including 20q gain, ERBB2 amplification and 15q loss. Copy number changes may provide prognostic information for DCIS recurrence, but validation in additional cohorts is required.
摘要
导管原位癌(DCIS)是浸润性乳腺癌的一种非特异性前驱性病变,在乳腺影像学检查中经常可以发现且需要治疗。高达25%的DCIS可以复发,并且复发病例中一半存在浸润,但是对于DCIS复发没有可靠的生物学标记。我们推测拷贝数目异常能够预测复发的可能性。我们选择一组仅进行了局部扩大手术切除的单纯性DCIS病例,采用Affymetrix OncoScan MIP微阵列技术对其广谱基因组进行拷贝数目以及杂合性缺失分析。这些病例包括7年内未复发的病例(n=25)和诊断1-5年后复发的病例(n=15)。单纯性DCIS在拷贝数目变化方面与浸润性乳腺癌具有广泛的相似性,除了DCIS中出现的更高频率ERBB2扩增,其他方面与浸润性乳腺癌一致。复发性与非复发性病例之间患者的年龄或ER状态无显著差异。总之,DCIS复发性病例较非复发性病例发生了更多拷贝数目事件。在拷贝数目增加频繁的复发性病例中,许多基因组区域增加的拷贝数目呈非随机性,包括20q的获得、ERBB2的扩增以及15q的缺失。拷贝数目变化可以为DCIS复发提供预后信息,但是需要在更多病例中得到验证。
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