一個由加拿大、英國,、美國的59名研究人員組成的國際研究小組最新發(fā)表的研究報告顯示,，他們從分子層面的研究發(fā)現(xiàn)，不同三陰乳腺癌腫瘤的基因組其實存在很大差異,，這也是常用藥物對這類癌癥療效不大的重要因素,，未來可能需要調(diào)整相關的治療手法。相關論文4月4日在線發(fā)表于《Nature》.
研究人員利用電腦技術分析了100個三陰乳腺癌腫瘤的基因組,，結果發(fā)現(xiàn)它們中沒有任何兩個相似,，更不用說完全一樣。研究人員說,，鑒于它們是臨床上同一類型的腫瘤,，這一結果出乎意料。
報告的作者之一,、加拿大西門菲沙大學教授史蒂文·瓊斯解釋說,，通過在分子層面觀察，發(fā)現(xiàn)上述腫瘤其實是一系列不同類型的乳腺癌腫瘤,，而并非原來認為的完全一樣,，新發(fā)現(xiàn)有助解釋三陰乳腺癌為何如此難治。
三陰乳腺癌約占所有乳腺癌病例中的16%,，特征是雌激素受體,、孕激素受體以及人表皮生長因子受體呈陰性。醫(yī)學界一直認為它是乳腺癌中最致命的類型,。
瓊斯說,，新研究發(fā)現(xiàn)證明有針對性的癌癥藥物治療非常重要，也就是說需要根據(jù)某一類型腫瘤的基因組成選用不同藥物進行治療,，而不是像以往那樣,，僅用一種治療手法應對所有類型的三陰乳腺癌腫瘤。（生物谷 bioon.com）
doi:10.1038/nature10933
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The clonal and mutational evolution spectrum of primary triple-negative breast cancers
Sohrab P. Shah,Andrew Roth,Rodrigo Goya,Arusha Oloumi,Gavin Ha,Yongjun Zhao,Gulisa Turashvili,Jiarui Ding,Kane Tse,Gholamreza Haffari,Ali Bashashati,Leah M. Prentice,Jaswinder Khattra,Angela Burleigh,Damian Yap,Virginie Bernard,Andrew McPherson,Karey Shumansky,Anamaria Crisan,Ryan Giuliany,Alireza Heravi-Moussavi,Jamie Rosner,Daniel Lai,Inanc Birol,Richard Varhol,Angela Tam,Noreen Dhalla,Thomas Zeng,Kevin Ma,Simon K. Chan,Malachi Griffith,Annie Moradian,S.-W. Grace Cheng,Gregg B. Morin,Peter Watson,Karen Gelmon,Stephen Chia,Suet-Feung Chin,Christina Curtis,Oscar M. Rueda,Paul D. Pharoah,Sambasivarao Damaraju,John Mackey,Kelly Hoon,Timothy Harkins,Vasisht Tadigotla,Mahvash Sigaroudinia,Philippe Gascard,Thea Tlsty,Joseph F. Costello,Irmtraud M. Meyer,Connie J. Eaves,Wyeth W. Wasserman,Steven Jones,David Huntsman,Martin Hirst,Carlos Caldas,Marco A. Marra& Samuel Aparicio
Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers1. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time—to our knowledge—in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC2, 3 showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes.
