Somatic mutations in ATRX in brain cancer

Patent metadata

Field	Value
Publication number	US-9982306-B2
Application number	US-201214129850-A
Country	US
Kind code	B2
Filing date	Jun 28, 2012
Priority date	Jun 29, 2011
Publication date	May 29, 2018
Grant date	May 29, 2018

Abstract

We determined the sequence of ATRX and DAXX in 447 cancers from various sites. We found mutations most commonly in pediatric glioblastoma multiformae (GBM) (11.1%), adult GBM (6.5%), oligodendrogliomas (7.7%) and medulloblastomas (1.5%); and showed that Alternative Lengthening of Telomeres (ALT), a telomerase-independent telomere maintenance mechanism found in cancers that have not activated telomerase, perfectly correlated with somatic mutations of either gene. In contrast, neuroblastomas, and adenocarcinomas of the ovary, breast, and pancreas were negative for mutations in ATRX and DAXX. Alterations in ATRX or DAXX define a specific molecular pathway that is closely associated with an alternative telomere maintenance function in human cancers.

First claim

The invention claimed is:

1. A method for testing a Central Nervous System (CNS) tumor in a patient, comprising:
testing the CNS tumor or cells shed from the tumor for the presence of an inactivating mutation in ATRX, by contacting the tumor or cells with an antibody which specifically binds to ATRX, wherein an ATRX inactivating mutation is detected.

2. A method for testing a Central Nervous System (CNS) tumor in a patient, comprising:
testing the CNS tumor or cells shed from the tumor for the presence of an inactivating mutation in ATRX, by contacting the tumor or cells with an antibody which specifically binds to ATRX, wherein the step of testing comprises an immunohistochemical analysis.

3. A method of comprising:
testing a tissue suspected of being a CNS tumor, or cells shed from the tissue by contacting the tissue or cells with an antibody which specifically binds to ATRX.

4. The method of claim 1 or 3 wherein the CNS tumor is a glial tumor.

5. The method of claim 1 or 3 wherein the CNS tumor is selected from the group consisting of: pediatric glioblastoma, adult glioblastoma, oligodendroglioma, medulloblastoma, anaplastic oligodendroglioma, oligoastrocytoma, anaplastic oligoastrocytoma, astrocytoma, and anaplastic astrocytoma.

6. The method of claim 1 , 2 or 3 wherein the mutation is selected from the group consisting of R2079X, Q1874X, Q1788H, E2277K, Q2156H, K455X, W263X, R2153C, and R1803H.

7. The method of claim 3 , wherein an ATRX inactivating mutation is detected.

Assignees

• Yan Hai
• Bigner Darell
• Vogelstein Bert
• Kinzler Kenneth W
• Meeker Alan
• Hruban Ralph
• Papadopoulos Nickolas
• Diaz Luis
• Jiao Yuchen
• Univ Duke
• Univ Johns Hopkins

Inventors

• Yan Hai
• Bigner Darell
• Vogelstein Bert
• Kinzler Kenneth W
• Meeker Alan
• Hruban Ralph
• Papadopoulos Nickolas
• Diaz Luis
• Jiao Yuchen

Classifications

• G01N33/57557

  of other specific parts of the body, e.g. brain · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12N15/1137

  against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138) · CPC title

• C07K16/40

  against enzymes · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title