Novel mutations target distinct subgroups of medulloblastoma
Giles W. Robinson,Matthew Parker,Tanya A. Kranenburg,Charles Lu,Charles Lu,Xiang Chen,Li Ding,Li Ding,Timothy N. Phoenix,Erin Hedlund,Lei Wei,Xiaoyan Zhu,Nader Chalhoub,Suzanne J. Baker,Robert Huether,Richard W. Kriwacki,Natasha Curley,Radhika Thiruvenkatam,Jianmin Wang,Gang Wu,Michael Rusch,Xin Hong,Xin Hong,Jared Becksfort,Pankaj Gupta,Jing Ma,John Easton,Bhavin Vadodaria,Arzu Onar-Thomas,Tong Lin,Shaoyi Li,Stanley Pounds,Steven W. Paugh,David Zhao,Daisuke Kawauchi,Martine F. Roussel,David Finkelstein,David W. Ellison,Ching C. Lau,Eric Bouffet,Tim Hassall,Tim Hassall,Sridharan Gururangan,Sridharan Gururangan,Richard J. Cohn,Richard J. Cohn,Robert S. Fulton,Robert S. Fulton,Lucinda L. Fulton,Lucinda L. Fulton,David J. Dooling,David J. Dooling,Kerri Ochoa,Kerri Ochoa,Amar Gajjar,Elaine R. Mardis,Richard K. Wilson,James R. Downing,Jinghui Zhang,Richard J. Gilbertson +59 more
TLDR
Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours identified genes that maintain this cell lineage (DDX3X), as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumorigenesis.Abstract:
Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma; several target distinct components of the epigenetic machinery in different disease subgroups, such as regulators of H3K27 and H3K4 trimethylation in subgroups 3 and 4 (for example, KDM6A and ZMYM3), and CTNNB1-associated chromatin re-modellers in WNT-subgroup tumours (for example, SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours identified genes that maintain this cell lineage (DDX3X), as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumorigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development.read more
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References
More filters
Journal ArticleDOI
Analyzing real-time PCR data by the comparative C(T) method.
TL;DR: This protocol provides an overview of the comparative CT method for quantitative gene expression studies and various examples to present quantitative gene Expression data using this method.
Book ChapterDOI
Primer3 on the WWW for general users and for biologist programmers.
Steve Rozen,Helen Skaletsky +1 more
TL;DR: This chapter assumes acquaintance with the principles and practice of PCR, as outlined in, for example, refs.
Journal ArticleDOI
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Tarjei S. Mikkelsen,Manching Ku,Manching Ku,David B. Jaffe,Biju Issac,Biju Issac,Erez Lieberman Aiden,Erez Lieberman Aiden,Georgia Giannoukos,Pablo Alvarez,William Brockman,Tae Kyung Kim,Richard Koche,Richard Koche,Richard Koche,William Lee,Eric M. Mendenhall,Eric M. Mendenhall,Aisling O'Donovan,Aviva Presser,Carsten Russ,Xiaohui Xie,Alexander Meissner,Marius Wernig,Rudolf Jaenisch,Chad Nusbaum,Eric S. Lander,Eric S. Lander,Bradley E. Bernstein,Bradley E. Bernstein +29 more
TL;DR: The application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells is reported and it is shown that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms.
Journal ArticleDOI
Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms
David Malkin,Frederick P. Li,Frederick P. Li,Louise C. Strong,Joseph F. Fraumeni,Camille E. Nelson,Camille E. Nelson,David H. Kim,Jayne Kassel,Magdalena A. Gryka,Farideh Z. Bischoff,Michael A. Tainsky,Stephen H. Friend +12 more
TL;DR: Germ line p53 mutations have been detected in all five LFS families analyzed and can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.
Journal ArticleDOI
Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
Ru Cao,Liangjun Wang,Hengbin Wang,Li Xia,Hediye Erdjument-Bromage,Paul Tempst,Richard S. Jones,Yi Zhang +7 more
TL;DR: The purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex, is reported, and it is demonstrated that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27).
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