US 20130296408A1

(19) United States

(12) Patent Application Publication (10) Pub. No.: US 2013/0296408 A1
Vogelstein et al. (43) Pub. Date: NOV. 7, 2013

(54) MEDULLOBLASTOMA GENES AS TARGETS Publication Classi?cation

FOR DIAGNOSIS AND THERAPEUTICS
(76) Inventors: Bert Vogelstein, Baltimore, MD (US);
Kenneth Kinzler, Baltimore, MD (US);
Nickolas Papadopoulos, Towson, MD
(US); Donald Williams Parsons,
Bellaire, TX (US); Rebecca J. Leary,
Baltimore, MD (US); Meng Li, San
Francisco, CA (U S); Xiaosong Zhang,
San Francisco, CA (US); Sian Jones,
Baltimore, MD (US); Gregory J.
Riggins, White Hall, MD (US); Victor
Velculescu, Dayton, MD (US)
(21) App1.No.: 13/884,154
(22) PCT Filed: Nov. 8, 2011
(86) PCT No.: PCT/US11/59751
§371(C)(1),
(2), (4) Date: Jul. 22, 2013
Related US. Application Data
(60) Provisional application No. 61/411,332, ?led on Nov.
8, 2010.
(51) Int. Cl.
C12Q 1/68 (2006.01)
(52) US, Cl,
CPC .................................. .. C12Q 1/6886 (2013.01)
UsPc ........................ .. 514/44 R; 435/611; 435/71
(57) ABSTRACT
Medulloblastoma (MB) is the most common malignant brain
tumor of children. To identify the genetic alterations in this
tumor type, we searched for copy number alterations using
high density microarrays and sequenced all known protein
coding genes and miRNA genes using Sanger sequencing.
We found that, on average, each tumor had 11 gene alter
ations, markedly fewer than in common adult cancers. In
addition to alterations in the Hedgehog and Wnt pathways,
our analysis led to the discovery of genes not previously
known to be altered in MBs. Most notably, inactivating muta
tions of the histone H3K4 trimethylase genes MLL2 or MLL3
were identi?ed in 16% of MB patients. These results demon
strate key differences between the genetic landscapes of adult
and childhood cancers, highlight dysregulation of develop
mental pathways as an important mechanism underlying
MBs, and identify a role for a speci?c type of histone methy
lation in human tumorigenesis.
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