Patent AU-2020204028-B2 (AU)
Title: Methods and Materials for Assessing Homologous Recombination Deficiency
Inventor: ABKEVICH VICTOR
IPC: C12Q1/68
Filed: 2020-06-17
Granted: 2022-08-18
Abstract: This document provides methods and materials involved in assessing samples (e.g., cancer 
cells) for the presence of homologous recombination deficiency (HRD) or an HRD signature.  
For example, methods and materials for determining whether or not a cell (e.g., a cancer cell) 
contains an HRD 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. Specifically the present invention relates to a method of 
predicting the status of BRCA1 and/or BRCA2 genes in a cancer cell, comprising: 
determining, in the cancer cell, the total number of Indicator CA Regions comprising 
Indicator LOH Regions, Indicator TAI Regions, and Indicator LST Regions in at least one 
pair of human chromosomes of the cancer cell, wherein 
(a) an Indicator LOH Region is an LOH Region that is longer than 1.5 megabases in length 
but shorter than the entire length of the respective chromosome within which the LOH 
Region is located; 
(b) an Indicator TAI Region is a TAI Region with allelic imbalance that (a) extends to one 
of the subtelomeres, (b) does not cross the centromere, and (c) is longer than 1.5 
megabases in length; 
(c) an Indicator LST is a copy number breakpoint along the length of a chromosome that is 
between two regions of at least 5 megabases in length after filtering out regions shorter 
than 4 megabases in length; and, 
diagnosing a patient in whose cancer cell the total number of CA Regions is greater than a 
reference value as having an increased likelihood of a deficiency in the BRCA1 and/or 
BRCA2 gene. The present invention further relates to a method of predicting the status of 
BRCA1 and/or BRCA2 genes in a cancer cell, comprising: determining, in the cancer cell, an 
average across a total number of each type of Indicator CA Regions comprising at least two 
types chosen from Indicator LOH Regions, Indicator TAI Regions, or Indicator LST Regions 
in at least one pair of human chromosomes of the cancer cell, wherein 
(a) an Indicator LOH Region is an LOH Region that is longer than 1.5 megabases in 
length but shorter than the entire length of the respective chromosome within which 
the LOH Region is located;
(b) Indicator TAI Region is a TAI Region with allelic imbalance that (a) extends to one 
of the subtelomeres, (b) does not cross the centromere, and (c) is longer than 1.5 
megabases in length; 
(c) an Indicator LST is a copy number breakpoint along the length of a chromosome that 
is between two regions of at least 5 megabases in length after filtering out regions 
shorter than 4 megabases in length; and, 
correlating the average across the total number of CA regions that is greater than a reference 
number with an increased likelihood of a deficiency in the BRCA1 or BRCA2 gene.
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