據(jù)11月13日PLoS Genetics上的一篇文章報(bào)道,，相對于癌癥基因組中沒有發(fā)生特定遺傳改變的宮頸癌患者，經(jīng)過標(biāo)準(zhǔn)的治療后,，發(fā)生遺傳變化的患者,，其復(fù)發(fā)風(fēng)險(xiǎn)增加了三倍或四倍。研究人員表示,，特殊的基因改變是疾病發(fā)展過程中產(chǎn)生治療抵抗的重要一步,。
宮頸癌是一種最常見的惡性疾病，影響著全世界的婦女,，也是癌癥相關(guān)死亡的一個(gè)主要原因,。研究人員希望這些遺傳改變能增加通過標(biāo)準(zhǔn)檢測方法得到的臨床數(shù)據(jù)信息。先前的研究表明,，子宮頸癌患者的癌細(xì)胞表現(xiàn)出大量的遺傳變化,，但是它們對疾病發(fā)展和治療抑制的重要性還不是很清楚。
通過全基因組掃描,，研究人員發(fā)現(xiàn),，一系列與癌癥標(biāo)記相關(guān)的生物過程丟失了一些特殊的基因。此外,，他們還識(shí)別了新的與化療和輻射抑制相關(guān)的位點(diǎn),，并描述了相關(guān)的基因。
這項(xiàng)研究對于理解宮頸癌的發(fā)展具有重要的作用,，作者強(qiáng)調(diào)該研究結(jié)果在用于臨床測試之前還需要作進(jìn)一步證實(shí),。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
