Mutation of epigenetic regulators TET2 and MLL3 in patients with HTLV-I-induced acute adult T-cell leukemia.

Molecular Cancer
Chien-Hung YehChristophe Nicot

Abstract

Epigenetic regulators play a critical role in the maintenance of specific chromatin domains in an active or repressed state. Disruption of epigenetic regulatory mechanisms is widespread in cancer cells and largely contributes to the transformation process through active repression of tumor suppressor genes. While mutations of epigenetic regulators have been reported in various lymphoid malignancies and solid cancers, mutation of these genes in HTLV-I-associated T-cell leukemia has not been investigated. Here we used whole genome next generation sequencing (NGS) of uncultured freshly isolated ATL samples and identified the presence of mutations in SUZ12, DNMT1, DNMT3A, DNMT3B, TET1, TET2, IDH1, IDH2, MLL, MLL2, MLL3 and MLL4. TET2 was the most frequently mutated gene, occurring in 32 % (10/31) of ATL samples analyzed. Interestingly, NGS revealed nonsense mutations accompanied by loss of heterozygosity (LOH) in TET2 and MLL3, which was further confirmed by cloning and direct sequencing of DNA from uncultured cells. Finally, direct sequencing of matched control and tumor samples revealed that TET2 mutation was present only in ATL tumor cells. Our results suggest that inactivation of MLL3 and TET2 may play an important role in the ...Continue Reading

References

Feb 24, 2005·American Journal of Hematology·Christophe Nicot
Dec 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kunihiro TsukasakiToshiki Watanabe
May 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jeongkyung LeeJae W Lee
Sep 9, 2010·Proceedings of the National Academy of Sciences of the United States of America·Joanna PancewiczChristophe Nicot
Mar 19, 2011·Leukemia·M J WalterT A Graubert
Jun 16, 2011·Blood·Ali BazarbachiOlivier Hermine
Jan 13, 2012·Nature Medicine·Panagiotis NtziachristosIannis Aifantis
Aug 18, 2012·Nature Reviews. Cancer·Alan H ShihRoss L Levine
Mar 25, 2014·Molecular Cell·Hans-Martin HerzAli Shilatifard
Sep 5, 2014·Molecular Cancer·Hassiba Chaib-MezragChristophe Nicot
Oct 5, 2014·The Lancet Oncology·Kenji Ishitsuka, Kazuo Tamura
Oct 17, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kunihiro Tsukasaki, Kensei Tobinai
Jul 15, 2015·Journal of Oncology·Christophe Nicot
Sep 13, 2015·Blood·Hiroo KatsuyaUNKNOWN ATL-Prognostic Index Project

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Citations

Sep 25, 2019·Leukemia & Lymphoma·Haibin ZhangXiaozhong Wang
Jun 1, 2018·Nature·Joseph A FraiettaJ Joseph Melenhorst
Dec 20, 2019·Retrovirology·Ramona MolesGenoveffa Franchini
Aug 22, 2017·Current Opinion in Virology·Lucy CookCharles Rm Bangham
Jun 23, 2021·Biochemical Society Transactions·Lan-Hsin WangShu-Ping Wang

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Methods Mentioned

BETA
PCR
biopsy
Exome Sequencing

Software Mentioned

GATK
PicardTools
CASAVA
SamTools
GATK Unified Genotyper
BWA

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