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词条 Tet methylcytosine dioxygenase 2
释义

  1. Function

  2. Clinical significance

  3. WIT pathway

  4. References

  5. Further reading

Tet methylcytosine dioxygenase 2 (TET2) is a human gene.[1] It resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies.

Function

TET2 encodes a protein that catalyzes the conversion of the modified DNA base methylcytosine to 5-hydroxymethylcytosine.

Clinical significance

Mutations in this gene were first identified in myeloid neoplasms with deletion or uniparental disomy at 4q24.[2] TET2 may also be a candidate for active DNA demethylation, the catalytic removal of the methyl group added to the fifth carbon on the cytosine base.

Somatic TET2 mutations are frequently observed in myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes including chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemias (AML) and secondary AML (sAML).[3]

TET2 mutations have prognostic value in cytogenetically normal acute myeloid leukemia (CN-AML). "Nonsense" and "frameshift" mutations in this gene are associated with poor outcome on standard therapies in this otherwise favorable-risk patient subset.[4]

Loss of function TET2 mutations may also have a possible causal role in atherogenesis as reported by Jaiswal S. et al.

[5]

WIT pathway

TET2 is mutated in 7%–23% of AML patients. Importantly, TET2 is mutated in a mutually exclusive manner with WT1, IDH1, and IDH2.[6] TET2 can be recruited by WT1, a sequence-specific zinc finger transcription factor, to its target genes and activates WT1-target genes by converting methylcytosine into 5-hydroxymethylcytosine at the genes’ promoters.[7] The WIT pathway might also be more broadly involved in suppressing tumor formation, as a number of non-hematopoietic malignancies appear to harbor mutations of WIT genes in a non-exclusive manner.[8]

References

1. ^{{cite web |title = Entrez Gene: Tet methylcytosine dioxygenase 1|url = https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=54790|accessdate = September 2012}}
2. ^{{Cite journal | last1 = Langemeijer | first1 = S. M. C. | last2 = Kuiper | first2 = R. P. | last3 = Berends | first3 = M. | last4 = Knops | first4 = R. | last5 = Aslanyan | first5 = M. G. | last6 = Massop | first6 = M. | last7 = Stevens-Linders | first7 = E. | last8 = Van Hoogen | first8 = P. | last9 = Van Kessel | first9 = A. G. | last10 = Raymakers | doi = 10.1038/ng.391 | first10 = R. A. P. | last11 = Kamping | first11 = E. J. | last12 = Verhoef | first12 = G. E. | last13 = Verburgh | first13 = E. | last14 = Hagemeijer | first14 = A. | last15 = Vandenberghe | first15 = P. | last16 = De Witte | first16 = T. | last17 = Van Der Reijden | first17 = B. A. | last18 = Jansen | first18 = J. H. | title = Acquired mutations in TET2 are common in myelodysplastic syndromes | journal = Nature Genetics | volume = 41 | issue = 7 | pages = 838–842 | year = 2009 | pmid = 19483684 | pmc = }}
3. ^{{Cite journal | last1 = Ko | first1 = M. | last2 = Huang | first2 = Y. | last3 = Jankowska | first3 = A. M. | last4 = Pape | first4 = U. J. | last5 = Tahiliani | first5 = M. | last6 = Bandukwala | first6 = H. S. | last7 = An | first7 = J. | last8 = Lamperti | first8 = E. D. | last9 = Koh | first9 = K. P. | doi = 10.1038/nature09586 | last10 = Ganetzky | first10 = R. | last11 = Liu | first11 = X. S. | last12 = Aravind | first12 = L. | last13 = Agarwal | first13 = S. | last14 = MacIejewski | first14 = J. P. | last15 = Rao | first15 = A. | title = Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2 | journal = Nature | volume = 468 | issue = 7325 | pages = 839–843 | year = 2010 | pmid = 21057493 | pmc =3003755 }}
4. ^{{Cite journal | last1 = Metzeler | first1 = K. H. | last2 = Maharry | first2 = K. | last3 = Radmacher | first3 = M. D. | last4 = Mrózek | first4 = K. | last5 = Margeson | first5 = D. | last6 = Becker | first6 = H. | last7 = Curfman | first7 = J. | last8 = Holland | first8 = K. B. | last9 = Schwind | first9 = S. | last10 = Whitman | doi = 10.1200/JCO.2010.32.7742 | first10 = S. P. | last11 = Wu | first11 = Y. -Z. | last12 = Blum | first12 = W. | last13 = Powell | first13 = B. L. | last14 = Carter | first14 = T. H. | last15 = Wetzler | first15 = M. | last16 = Moore | first16 = J. O. | last17 = Kolitz | first17 = J. E. | last18 = Baer | first18 = M. R. | last19 = Carroll | first19 = A. J. | last20 = Larson | first20 = R. A. | last21 = Caligiuri | first21 = M. A. | last22 = Marcucci | first22 = G. | last23 = Bloomfield | first23 = C. D. | title = TET2 Mutations Improve the New European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study | journal = Journal of Clinical Oncology | volume = 29 | issue = 10 | pages = 1373–1381 | year = 2011 | pmid = 21343549 | pmc =3084003 }}
5. ^{{Cite journal | last1 = Jaiswal | first1 = S. |display-authors=etal | doi = 10.1056/NEJMoa170719 | title = Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease| journal = New England Journal of Medicine | volume = 377| issue = 2| pages = 111–121| year = 2017| pmid = 28636844}}
6. ^{{cite journal |vauthors=Rampal R, Alkalin A, Madzo J, Vasanthakumar A, Pronier E, Patel J, Li Y, Ahn J, Abdel-Wahab O, Shih A, Lu C, Ward PS, Tsai JJ, Hricik T, Tosello V, Tallman JE, Zhao X, Daniels D, Dai Q, Ciminio L, Aifantis I, He C, Fuks F, Tallman MS, Ferrando A, Nimer S, Paietta E, Thompson CB, Licht JD, Mason CE, Godley LA, Melnick A, Figueroa ME, Levine RL |title = DNA Hydroxymethylation Profiling Reveals that WT1 Mutations Result in Loss of TET2 Function in Acute Myeloid Leukemia|journal = Cell Rep|volume = 9|issue = 5|pages = 1841–56|date = December 2014|pmid = 25482556|doi = 10.1016/j.celrep.2014.11.004|pmc=4267494}}
7. ^{{cite journal |vauthors=Wang Y, Xiao M, Chen X, Chen L, Xu Y, Lv L, Wang P, Yang H, Ma S, Lin H, Jiao B, Ren R, Ye D, Guan KL, Xiong Y |title = WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation|journal = Mol Cell|volume = 57|issue = 4|pages = 662–73|date = February 2015|pmid = 25601757|doi = 10.1016/j.molcel.2014.12.023|pmc=4336627}}
8. ^{{Cite journal|url = |title = A new path to leukemia with WIT|vauthors=Sardina JL, Graf T |date = February 2015|journal = Mol Cell|doi = 10.1016/j.molcel.2015.02.005|pmid = 25699704|access-date =|volume=57|pages=573–4}}

Further reading

{{refbegin | 2}}
  • {{Cite journal

| last1 = Langemeijer | first1 = S. M. C.
| last2 = Kuiper | first2 = R. P.
| last3 = Berends | first3 = M.
| last4 = Knops | first4 = R.
| last5 = Aslanyan | first5 = M. G.
| last6 = Massop | first6 = M.
| last7 = Stevens-Linders | first7 = E.
| last8 = Van Hoogen | first8 = P.
| last9 = Van Kessel | first9 = A. G.
| last10 = Raymakers
| doi = 10.1038/ng.391 | first10 = R. A. P.
| last11 = Kamping | first11 = E. J.
| last12 = Verhoef | first12 = G. E.
| last13 = Verburgh | first13 = E.
| last14 = Hagemeijer | first14 = A.
| last15 = Vandenberghe | first15 = P.
| last16 = De Witte | first16 = T.
| last17 = Van Der Reijden | first17 = B. A.
| last18 = Jansen | first18 = J. H.
| title = Acquired mutations in TET2 are common in myelodysplastic syndromes
| journal = Nature Genetics
| volume = 41
| issue = 7
| pages = 838–842
| year = 2009
| pmid = 19483684
| pmc =
}}
  • {{Cite journal

| last1 = Ko | first1 = M.
| last2 = Huang | first2 = Y.
| last3 = Jankowska | first3 = A. M.
| last4 = Pape | first4 = U. J.
| last5 = Tahiliani | first5 = M.
| last6 = Bandukwala | first6 = H. S.
| last7 = An | first7 = J.
| last8 = Lamperti | first8 = E. D.
| last9 = Koh | first9 = K. P.
| doi = 10.1038/nature09586
| last10 = Ganetzky | first10 = R.
| last11 = Liu | first11 = X. S.
| last12 = Aravind | first12 = L.
| last13 = Agarwal | first13 = S.
| last14 = MacIejewski | first14 = J. P.
| last15 = Rao | first15 = A.
| title = Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2
| journal = Nature
| volume = 468
| issue = 7325
| pages = 839–843
| year = 2010
| pmid = 21057493
| pmc =3003755
}}
  • {{Cite journal

| last1 = Metzeler | first1 = K. H.
| last2 = Maharry | first2 = K.
| last3 = Radmacher | first3 = M. D.
| last4 = Mrózek | first4 = K.
| last5 = Margeson | first5 = D.
| last6 = Becker | first6 = H.
| last7 = Curfman | first7 = J.
| last8 = Holland | first8 = K. B.
| last9 = Schwind | first9 = S.
| last10 = Whitman
| doi = 10.1200/JCO.2010.32.7742 | first10 = S. P.
| last11 = Wu | first11 = Y. -Z.
| last12 = Blum | first12 = W.
| last13 = Powell | first13 = B. L.
| last14 = Carter | first14 = T. H.
| last15 = Wetzler | first15 = M.
| last16 = Moore | first16 = J. O.
| last17 = Kolitz | first17 = J. E.
| last18 = Baer | first18 = M. R.
| last19 = Carroll | first19 = A. J.
| last20 = Larson | first20 = R. A.
| last21 = Caligiuri | first21 = M. A.
| last22 = Marcucci | first22 = G.
| last23 = Bloomfield | first23 = C. D.
| title = TET2 Mutations Improve the New European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
| journal = Journal of Clinical Oncology
| volume = 29
| issue = 10
| pages = 1373–1381
| year = 2011
| pmid = 21343549
| pmc =3084003
}}{{refend}}{{Use dmy dates|date=April 2017}}

1 : Genes on human chromosome 4
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