近日,,梅奧診所研究人員已經發(fā)現了一種乳腺癌新的分子突變類型,這一發(fā)現可能有助于理解對不同類型的乳腺腫瘤的發(fā)展和生長,。相關研究人員說:RNA的突變形式--融合基因轉錄可以確定腫瘤的亞型,并提供新的策略來對抗癌癥。
他們的研究發(fā)表在4月15日的Cancer Research雜志上,,該研究是首次系統(tǒng)地研究與不同類型乳腺腫瘤相關的融合基因和融合基因轉錄。
目前腫瘤學家了解到乳腺癌的三個基本類型:雌激素受體(ER)陽性,、HER-2陽性和三陰乳腺癌,。
佛羅里達州梅奧診所的綜合癌癥中心和乳腺癌的轉化基因組計劃研究人員Edith Perez MD說:但實際情況是乳腺癌很復雜,遠不止這三種亞型,,治療乳腺癌的挑戰(zhàn)之一是找出能預測乳腺癌對特定治療有如何反應的基因標記物,。
她說:有關乳腺癌亞型特異性融合基因的發(fā)現向尋找基因標記物邁出了一大步,,我們的研究結果表明融合基因在乳腺癌是很常見的,比我們想象的還要常見,。這些融合基因代表了乳腺癌中基因突變事件,,但其在乳腺癌中的作用目前還不了解。
E. Aubrey Thompson博士表示:融合基因能產生與腫瘤發(fā)展,、生長以及治療敏感性有關的蛋白質,,所以我們了解了一套新的基因組變化情況,這幫助我們了解治療乳腺癌的一種新方式,。
有關這項新發(fā)現現在還需要開展更多研究,,他說:我們需要進一步了解這些融合基因和蛋白質發(fā)揮的作用。
Thompson博士說:腫瘤細胞的顯著特性之一不能修復損壞的基因缺陷,。
這些突變蛋白可能有一個全新的促進癌癥作用,,或者他們可能會干擾正常細胞的功能。”
血癌如白血病和淋巴瘤中常見融合基因,。然而,,在這一發(fā)現之前,很少有人在實體如乳腺癌腫瘤中發(fā)現融合基因,。
Perez博士說:因為融合基因,、轉錄以及蛋白質一般只在腫瘤中被發(fā)現,他們制造出鑒別腫瘤細胞的理想生物標志物,。
她說,,此外融合基因產生的蛋白質可能與腫瘤生長相關,這一點已經在血液癌癥和肺癌中被觀察到,。
這項研究部分由國家佛羅里達州Bankhead-Coley項目,、乳腺癌研究基金會、Donna基金會,、Carmichael Family基金會,、美國國家癌癥研究所,梅奧基金會資助,。
梅奧診所簡介:世界著名私立非營利性醫(yī)療機構,,于1864年由梅奧醫(yī)生在明尼蘇達州羅切斯特市創(chuàng)建,是世界最具影響力和代表世界最高醫(yī)療水平的醫(yī)療機構之一,,在醫(yī)學研究領域處于領跑者地位,。(生物谷:Bioon.com)
doi:10.1158/0008-5472.CAN-11-3142
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PMID:
Detection of Redundant Fusion Transcripts as Biomarkers or Disease-Specific Therapeutic Targets in Breast Cancer
Yan W. Asmann, Brian M. Necela, Krishna R. Kalari, Asif Hossain, Tiffany R. Baker, Jennifer M. Carr, Caroline Davis, et al.
Fusion genes and fusion gene products are widely employed as biomarkers and therapeutic targets in hematopoietic cancers, but their applications have yet to be appreciated in solid tumors. Here, we report the use of SnowShoes-FTD, a powerful new analytic pipeline that can identify fusion transcripts and assess their redundancy and tumor subtype-specific distribution in primary tumors. In a study of primary breast tumors, SnowShoes-FTD was used to analyze paired-end mRNA-Seq data from a panel of estrogen receptor (ER)+, HER2+, and triple-negative primary breast tumors, identifying tumor-specific fusion transcripts by comparison with mRNA-Seq data from nontransformed human mammary epithelial cell cultures plus the Illumina Body Map data from normal tissues. We found that every primary breast tumor that was analyzed expressed one or more fusion transcripts. Of the 131 tumor-specific fusion transcripts identified, 86 were “private” (restricted to a single tumor) and 45 were “redundant” (distributed among multiple tumors). Among the redundant fusion transcripts, 7 were unique to ER+ tumors and 8 were unique to triple-negative tumors. In contrast, none of the redundant fusion transcripts were unique to HER2+ tumors. Both private and redundant fusion transcripts were widely expressed in primary breast tumors, with many mapping to genomic loci implicated in breast carcinogenesis and/or risk. Our finding that some fusion transcripts are tumor subtype-specific suggests that these entities may be critical determinants in the etiology of breast cancer subtypes, useful as biomarkers for tumor stratification, or exploitable as cancer-specific therapeutic targets.