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248) Unbiased genetic forward screening using retroviral insertional mutagenesis in a genetically engineered mouse model of human multiple myeloma may further our understanding of the genetic pathways that govern neoplastic plasma cell development.
* WDR26 and MTF2 are therapeutic targets in multiple myeloma.
- Unbiased genetic forward screening using retroviral insertional mutagenesis in a genetically engineered mouse model of human multiple myeloma may further our understanding of the genetic pathways that govern neoplastic plasma cell development. To evaluate this hypothesis, we performed a tumor induction study in MYC-transgenic mice infected as neonates with the Moloney-derived murine leukemia virus, MOL4070LTR. Next-generation DNA sequencing of proviral genomic integration sites yielded rank-ordered candidate tumor progression genes that accelerated plasma cell neoplasia in mice. Rigorous clinical and biological validation of these genes led to the discovery of two novel myeloma genes: WDR26 (WD repeat-containing protein 26) and MTF2 (metal response element binding transcription factor 2). WDR26, a core component of the carboxy-terminal to LisH (CTLH) complex, is overexpressed or mutated in solid cancers. MTF2, an ancillary subunit of the polycomb repressive complex 2 (PRC2), is a close functional relative of PHD finger protein 19 (PHF19) which is currently emerging as an important driver of myeloma. These findings underline the utility of genetic forward screens in mice for uncovering novel blood cancer genes and suggest that WDR26-CTLH and MTF2-PRC2 are promising molecular targets for new approaches to myeloma treatment and prevention.
=>1.さらにずっと, さらに先に, 一層遠く, その上, 更に, もっと遠い, なお一層の, さらに遠く,
もっと先に, いっそうはるかに, さらにまた, さらになお(furthermore), 2.進める, 助成する, 促進する
Overview of verb further
The verb further has 2 senses (first 2 from tagged texts)
1. (7) foster, further -- (promote the growth of; "Foster our children's well-being and education")
2. (2) promote, advance, boost, further, encourage -- (contribute to the progress or growth of; "I
am promoting the use of computers in the classroom")
Overview of adj further
The adj further has 1 sense (first 1 from tagged texts)
1. (2) further, farther -- (more distant in especially degree; "nothing could be further from the
truth"; "further from our expectations"; "farther from the truth"; "farther from our expectations")
Overview of adv further
The adv further has 3 senses (first 3 from tagged texts)
1. (33) further, farther -- (to or at a greater extent or degree or a more advanced stage (`further'
is used more often than `farther' in this abstract sense); "further complicated by uncertainty about
the future"; "let's not discuss it further"; "nothing could be further from the truth"; "they are
further along in their research than we expected"; "the application of the law was extended
farther"; "he is going no farther in his studies")
2. (10) further -- (in addition or furthermore; "if we further suppose"; "stated further that he
would not cooperate with them"; "they are definitely coming; further, they should be here already")
3. (1) farther, further -- (to or at a greater distance in time or space (`farther' is used more
frequently than `further' in this physical sense); "farther north"; "moved farther away"; "farther
down the corridor"; "the practice may go back still farther to the Druids"; "went only three miles
further"; "further in the future")
Overview of adv far
The adv far has 5 senses (first 4 from tagged texts)
1. (61) far -- (to a considerable degree; very much; "a far far better thing that I do"; "felt far
worse than yesterday"; "eyes far too close together")
2. (39) far -- (at or to or from a great distance in space; "he traveled far"; "strayed far from
home"; "sat far away from each other")
3. (22) far -- (at or to a certain point or degree; "I can only go so far before I have to give up";
"how far can we get with this kind of argument?")
4. (3) far -- (remote in time; "if we could see far into the future"; "all that happened far in the
past")
5. far -- (to an advanced stage or point; "a young man who will go very far")
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