Biomarkers for non-hodgkin lymphomas and uses thereof

Inactive Publication Date: 2013-04-25
BRITISH COLUMBIA CANCER AGENCY BRANCH
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  • Application Information

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Benefits of technology

The patent text describes the identification of biomarkers that can help identify and classify specific types of B-cell NHL, a type of cancer. These biomarkers have been found to be mutated in tumour samples from individuals with B-cell NHL and show evidence of positive selection. By using these biomarkers, it becomes possible to better manage and treat the disease with specific therapies based on the particular subtype of cancer.

Problems solved by technology

Current knowledge of the specific genetic events leading to DLBCL and FL is limited to the presence of a few recurrent genetic abnormalities [2].
Despite the disparity in response to therapy of the individual subtypes and the knowledge of clear genetic differences between the subtypes, clearly identifying B-cell NHLs remains challenging.

Method used

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  • Biomarkers for non-hodgkin lymphomas and uses thereof
  • Biomarkers for non-hodgkin lymphomas and uses thereof
  • Biomarkers for non-hodgkin lymphomas and uses thereof

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example 1

Identification of Recurrently Mutated Genes

[0051]The genomes or exomes of 14 NHL cases were sequenced, all with matched constitutional DNA sequenced to comparable depths. After screening for single nucleotide variants followed by subtraction of known polymorphisms and visual inspection of the sequence read alignments, 717 nonsynonymous (coding single nucleotide variants; cSNVs) affecting 651 genes were identified. Between 20 and 135 cSNVs in each of these genomes were identified. Only 25 of the 651 genes with cSNVs were represented in the cancer gene census (December, 2010 release) [14].

[0052]RNA sequencing (RNA-seq) was performed on these 14 NHL cases and an expanded set of 113 samples comprising 83 DLBCL, 12 FL and 8 B-cell NHL cases with other histologies and 10 DLBCL-derived cell lines. These data were analysed to identify novel fusion transcripts and cSNVs (FIG. 1). 240 genes were identified with at least one cSNV in a genome / exome or an RNA-seq “mutation hot spot” (below), and...

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Abstract

The disclosure provides a method of identifying a subject as having B-cell non-Hodgkin lymphoma (NHL) such as testing a sample from a subject for a mutation in one or more biomarkers. Also described are methods for classifying or monitoring a subject having, or suspected of having, B-cell non-Hodgkin lymphoma comprising testing the sample for a mutation in one or more biomarkers.

Description

RELATED APPLICATIONS[0001]This is a Patent Cooperation Treaty Application which claims the benefit of 35 U.S.C. 119 based on the priority of corresponding U.S. Provisional Patent Application No. 61 / 357,813 filed Jun. 23, 2010, and U.S. Provisional Application No. 61 / 420,065 filed Dec. 6, 2010, the contents of which are incorporated herein in their entirety.FIELD OF THE DISCLOSURE[0002]The disclosure relates to methods of testing for cancer and more specifically to methods of testing samples for somatic mutations indicative of B-cell Non-Hodgkin Lymphomas (NHLs).BACKGROUND OF THE DISCLOSURE[0003]Non-Hodgkin lymphomas (NHLs) are cancers of B, T or natural killer lymphocytes. The two most common types of NHL, follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), together comprise 60% of new B-cell NHL diagnoses each year in North America [1]. FL is an indolent and typically incurable disease characterized by clinical and genetic heterogeneity. DLBCL is aggressive and like...

Claims

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Application Information

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IPC IPC(8): C12Q1/68
CPCC12Q1/6886C12Q2600/106C12Q2600/112G01N33/57407G01N33/57426C07K14/705C12Q2600/156C40B30/04
Inventor MORIN, RYAN D.MARRA, MARCO A.MUNGALL, ANDREW J.HIRST, MARTINMENDEZ-LAGO, MARIAGASCOYNE, RANDY D.CONNORS, JOSEPH M.
Owner BRITISH COLUMBIA CANCER AGENCY BRANCH
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