近日,，梅奧診所研究人員已經(jīng)發(fā)現(xiàn)了一種乳腺癌新的分子突變類型,，這一發(fā)現(xiàn)可能有助于理解對(duì)不同類型的乳腺腫瘤的發(fā)展和生長。相關(guān)研究人員說：RNA的突變形式--融合基因轉(zhuǎn)錄可以確定腫瘤的亞型,，并提供新的策略來對(duì)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(guān)的融合基因和融合基因轉(zhuǎn)錄。
目前腫瘤學(xué)家了解到乳腺癌的三個(gè)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(dá)州梅奧診所的綜合癌癥中心和乳腺癌的轉(zhuǎn)化基因組計(jì)劃研究人員Edith Perez MD說：但實(shí)際情況是乳腺癌很復(fù)雜,，遠(yuǎn)不止這三種亞型，治療乳腺癌的挑戰(zhàn)之一是找出能預(yù)測(cè)乳腺癌對(duì)特定治療有如何反應(yīng)的基因標(biāo)記物,。
她說：有關(guān)乳腺癌亞型特異性融合基因的發(fā)現(xiàn)向?qū)ふ一驑?biāo)記物邁出了一大步,，我們的研究結(jié)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(chǎn)生與腫瘤發(fā)展,、生長以及治療敏感性有關(guān)的蛋白質(zhì)，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(guān)這項(xiàng)新發(fā)現(xiàn)現(xiàn)在還需要開展更多研究,，他說：我們需要進(jìn)一步了解這些融合基因和蛋白質(zhì)發(fā)揮的作用,。
Thompson博士說：腫瘤細(xì)胞的顯著特性之一不能修復(fù)損壞的基因缺陷。
這些突變蛋白可能有一個(gè)全新的促進(jìn)癌癥作用,，或者他們可能會(huì)干擾正常細(xì)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(xiàn)之前,，很少有人在實(shí)體如乳腺癌腫瘤中發(fā)現(xiàn)融合基因,。
Perez博士說：因?yàn)槿诤匣?、轉(zhuǎn)錄以及蛋白質(zhì)一般只在腫瘤中被發(fā)現(xiàn),，他們制造出鑒別腫瘤細(xì)胞的理想生物標(biāo)志物,。
她說,，此外融合基因產(chǎn)生的蛋白質(zhì)可能與腫瘤生長相關(guān),，這一點(diǎn)已經(jīng)在血液癌癥和肺癌中被觀察到。
這項(xiàng)研究部分由國家佛羅里達(dá)州Bankhead-Coley項(xiàng)目,、乳腺癌研究基金會(huì),、Donna基金會(huì)、Carmichael Family基金會(huì),、美國國家癌癥研究所,，梅奧基金會(huì)資助。
梅奧診所簡(jiǎn)介：世界著名私立非營利性醫(yī)療機(jī)構(gòu),，于1864年由梅奧醫(yī)生在明尼蘇達(dá)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(jī)構(gòu)之一，在醫(yī)學(xué)研究領(lǐng)域處于領(lǐng)跑者地位。（生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-11-3142
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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.
