据11月13日PLoS Genetics上的一篇文章报道,相对于癌症基因组中没有发生特定遗传改变的宫颈癌患者,经过标准的治疗后,发生遗传变化的患者,其复发风险增加了三倍或四倍。研究人员表示,特殊的基因改变是疾病发展过程中产生治疗抵抗的重要一步。
宫颈癌是一种最常见的恶性疾病,影响着全世界的妇女,也是癌症相关死亡的一个主要原因。研究人员希望这些遗传改变能增加通过标准检测方法得到的临床数据信息。先前的研究表明,子宫颈癌患者的癌细胞表现出大量的遗传变化,但是它们对疾病发展和治疗抑制的重要性还不是很清楚。
通过全基因组扫描,研究人员发现,一系列与癌症标记相关的生物过程丢失了一些特殊的基因。此外,他们还识别了新的与化疗和辐射抑制相关的位点,并描述了相关的基因。
这项研究对于理解宫颈癌的发展具有重要的作用,作者强调该研究结果在用于临床测试之前还需要作进一步证实。(生物谷Bioon.com)
生物谷推荐原始出处:
PLoS Genet 5(11): e1000719. doi:10.1371/journal.pgen.1000719
Gene Dosage, Expression, and Ontology Analysis Identifies Driver Genes in the Carcinogenesis and Chemoradioresistance of Cervical Cancer
Malin Lando1, Marit Holden2, Linn C. Bergersen3, Debbie H. Svendsrud1, Trond Stokke1, Kolbein Sundf?r4, Ingrid K. Glad3, Gunnar B. Kristensen4,5, Heidi Lyng1*
1 Department of Radiation Biology, Norwegian Radium Hospital, Oslo, Norway, 2 Norwegian Computing Center, Oslo, Norway, 3 Department of Mathematics, University of Oslo, Oslo, Norway, 4 Department of Gynecologic Oncology, Norwegian Radium Hospital, Oslo, Norway, 5 Department of Medical Informatics, University of Oslo, Oslo, Norway
Integrative analysis of gene dosage, expression, and ontology (GO) data was performed to discover driver genes in the carcinogenesis and chemoradioresistance of cervical cancers. Gene dosage and expression profiles of 102 locally advanced cervical cancers were generated by microarray techniques. Fifty-two of these patients were also analyzed with the Illumina expression method to confirm the gene expression results. An independent cohort of 41 patients was used for validation of gene expressions associated with clinical outcome. Statistical analysis identified 29 recurrent gains and losses and 3 losses (on 3p, 13q, 21q) associated with poor outcome after chemoradiotherapy. The intratumor heterogeneity, assessed from the gene dosage profiles, was low for these alterations, showing that they had emerged prior to many other alterations and probably were early events in carcinogenesis. Integration of the alterations with gene expression and GO data identified genes that were regulated by the alterations and revealed five biological processes that were significantly overrepresented among the affected genes: apoptosis, metabolism, macromolecule localization, translation, and transcription. Four genes on 3p (RYBP, GBE1) and 13q (FAM48A, MED4) correlated with outcome at both the gene dosage and expression level and were satisfactorily validated in the independent cohort. These integrated analyses yielded 57 candidate drivers of 24 genetic events, including novel loci responsible for chemoradioresistance. Further mapping of the connections among genetic events, drivers, and biological processes suggested that each individual event stimulates specific processes in carcinogenesis through the coordinated control of multiple genes. The present results may provide novel therapeutic opportunities of both early and advanced stage cervical cancers.