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Methods and materials for assessing loss of heterozygosity

a heterozygosity and heterozygosity technology, applied in the field of methods and materials for assessing the loss of heterozygosity, can solve the problem of serious public health problems such as cancer, and achieve the effect of increasing the likelihood of cancer

Inactive Publication Date: 2012-01-19
MYRIAD GENETICS +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]Determining whether or not cancer patients are likely to respond to a particular cancer treatment regimen as described herein can allow patients and clinicians to proceed with a treatment regimen having an increased likelihood of treating cancer (e.g., reducing the number of cancer cells within a patient). In some cases, determining whether or not cancer patients are likely to respond to a particular cancer treatment regimen as described herein can allow patients and clinicians to select the most effective initial cancer treatment regimen for that patient.
[0014]In another aspect, this document features a method of predicting a cancer patient's response to a cancer treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase I inhibitor, radiation, and / or a PARP inhibitor. The method comprises, or consists essentially of, determining, in a cancer cell from the cancer patient, the number of LOH regions in at least one pair of human chromosomes of a cancer cell of the cancer patient that are longer than a first length but shorter than the length of the whole chromosome containing the LOH region, wherein the at least one pair of human chromosomes is not a human X / Y sex chromosome pair, wherein the first length is about 1.5 or more megabases; and correlating the total number that is greater than a reference number with an increased likelihood that the cancer patient will respond to the cancer treatment regimen.

Problems solved by technology

Cancer is a serious public health problem, with 562,340 people in the United States of America dying of cancer in 2009 alone.
One of the primary challenges in cancer treatment is discovering relevant, clinically useful characteristics of a patient's own cancer and then, based on these characteristics, administering a treatment plan best suited to the patient's cancer.

Method used

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  • Methods and materials for assessing loss of heterozygosity
  • Methods and materials for assessing loss of heterozygosity
  • Methods and materials for assessing loss of heterozygosity

Examples

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example 1

Assessing LOH Regions and HDR

[0119]Two sets of tumors were used from advanced ovarian cancer patients. The first set of 94 tumors (training set) was used to derive a candidate signature, and the second set of 40 tumors (validation set) was used to validate the signature. All coding regions of BRCA1 and BRCA2 genes were sequenced to detect germ line and somatic mutations. Levels of BRCA1 and BRCA2 mRNA expression were measured, and Affymetrix SNP microarrays were performed.

[0120]A computer program was used to reconstruct LOH signature status based on allele intensities derived from the microarray data. An algorithm was developed and implemented as a computer program to reconstruct LOH regions based on genotype (e.g., SNP genotype) data.

[0121]One point of the algorithm was to first reconstruct allele specific copy numbers (ASCN) at each locus (e.g., SNP). ASCNs are the numbers of copies of both paternal and maternal alleles. An LOH region was then determined as a stretch of SNPs with ...

example 2

Chemo Toxicity Responses

[0129]In preparation of chemo toxicity response experiments, all cell lines were grown at 37° C. plus 5% CO2 in 75 cm2 tissue culture flasks (VWR International, Inc. Cat # 353136) and the recommended growth medium. Before performing each experiment, each cell line was trypsinized (Invitrogen Corporation Cat # 25200-056), counted, and seeded in Advanced RPMI 1640 (Invitrogen Corporation Cat # 12633-020), 3% FBS, 1% penicillin / streptomycin (Invitrogen Corporation Cat # 15140-122) at 2500 cells or 5000 cells in 100 μL media per well from columns 2-12 of 96-well polystyrene microplates with clear bottom (Perkin Elmer Cat #6005181), leaving column 1 with 100 μL per well of media only. The cell-seeded plates were then incubated at 37° C. plus 5% CO2 overnight.

[0130]Two different final drug concentration working stocks were prepared. In cases where 100% DMSO was required for drug solubility, Advanced RPMI 1640 was used as the diluent for the highest concentration. A...

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Abstract

This document provides methods and materials involved in assessing samples (e.g., cancer cells) for the presence of a loss of heterozygosity (LOH) signature. For example, methods and materials for determining whether or not a cell (e.g., a cancer cell) contains an LOH signature are provided. Materials and methods for identifying cells (e.g., cancer cells) having a deficiency in homology directed repair (HDR) as well as materials and methods for identifying cancer patients likely to respond to a particular cancer treatment regimen also are provided.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is claims priority to U.S. Provisional Patent Application Ser. No. 61 / 356,501 filed Jun. 18, 2010, the entire contents of which are hereby incorporated by reference.BACKGROUND[0002]1. Technical Field[0003]This document relates to methods and materials involved in assessing samples (e.g., cancer cells) for the presence of a loss of heterozygosity (LOH) signature. For example, this document provides methods and materials for determining whether or not a cell (e.g., a cancer cell) contains an LOH signature. This document also provides materials and methods for identifying cells (e.g., cancer cells) having a deficiency in homology directed repair (HDR) as well as materials and methods for identifying cancer patients likely to respond to a particular cancer treatment regimen.[0004]2. Background Information[0005]Cancer is a serious public health problem, with 562,340 people in the United States of America dying of cancer in 200...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K33/24A61K31/28A61K31/704A61P35/00A61K31/166A61K31/501A61K31/4184C12Q1/68A61K31/4375G16B20/10G16B20/20
CPCC12Q1/6827C12Q1/6886C12Q2600/106C12Q2600/136C12Q2600/16G06F19/18C12Q2600/158C12Q2600/156C12Q2537/16G16B20/00A61P35/00G16B20/20G16B20/10C12Q2527/127C12Q2565/00G16H20/00
Inventor ABKEVICH, VICTORGUTIN, ALEXANDERTIMMS, KIRSTENLANCHBURY, JERRY
Owner MYRIAD GENETICS
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