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1p36缺失是微卫星稳定的II-III期结肠癌肿瘤播散的一个标志物。

1p36 deletion is a marker for tumour dissemination in microsatellite stable stage II-III colon cancer.

作者信息

Mayrhofer Markus, Kultima Hanna Göransson, Birgisson Helgi, Sundström Magnus, Mathot Lucy, Edlund Karolina, Viklund Björn, Sjöblom Tobias, Botling Johan, Micke Patrick, Påhlman Lars, Glimelius Bengt, Isaksson Anders

机构信息

Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Box 3056, Uppsala 750 03, Sweden.

出版信息

BMC Cancer. 2014 Nov 24;14:872. doi: 10.1186/1471-2407-14-872.

Abstract

BACKGROUND

The clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination.

METHODS

Follow-up was at least 5 years for stage II-III patients without distant recurrence. Affymetrix SNP 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. Fisher's exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage IV) or later as recurrent disease (stage II-III).

RESULTS

Loss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage II-IV (odds ratio = 5.5). It was enriched to a similar extent in tumours with distant recurrence within stage II and stage III subgroups, and may therefore be used as a prognostic marker at diagnosis. Loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. Therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. The association with tumour dissemination was supported by independent data from the The Cancer Genome Atlas.

CONCLUSION

Deletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages II and III.

摘要

背景

结肠癌的临床行为具有异质性。所有分期患者的五年总生存率为50 - 65%。已鉴定出复发性体细胞染色体改变,其中一些已显示出作为肿瘤播散标志物的潜力,而肿瘤播散是大多数结肠癌死亡的原因。我们研究了115例选定的II - IV期原发性结肠癌,以探讨染色体改变与肿瘤播散之间的关联。

方法

对无远处复发的II - III期患者进行至少5年的随访。使用Affymetrix SNP 6.0微阵列和等位基因特异性拷贝数分析来鉴定染色体改变。采用Fisher精确检验将改变与在诊断时(IV期)或后来作为复发性疾病(II - III期)检测到的肿瘤播散相关联。

结果

1p36.11 - 21缺失与II - IV期微卫星稳定肿瘤的肿瘤播散相关(优势比 = 5.5)。在II期和III期亚组内有远处复发的肿瘤中,其富集程度相似,因此可在诊断时用作预后标志物。相对于基因组平均拷贝数的1p36.11 - 21缺失与拷贝数绝对缺失相比显示出相似的预后价值。因此,使用相对缺失作为预后标志物将通过也应用于超二倍体癌症基因组而使更多患者受益。来自癌症基因组图谱的独立数据支持了与肿瘤播散的关联。

结论

1p36缺失可用于指导II期和III期微卫星稳定结肠癌的辅助治疗决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eeaa/4251789/32afb8bf23c3/12885_2014_5046_Fig1_HTML.jpg

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