CURIE LUNG CANCER Copy Number Alteration Analysis

This document summarizes procedures for generating Curie Lung cancer copy number alteration data output. Data analysis has been performed by informatics group at Curie Institute.

Analysis

PDX were profiled using Affymetrix genomics array with SNP 6.0 or with Cytoscan HD array. Genome-wide copy number analysis was conducted by means of Affymetrix SNP arrays, as previously described (Laurent et al.,2013 and Crepin et al. 2017).

500 and 250ng of gDNA was respectively used for SNP 6.0 and Cytoscan HD as starting material as recommended by the supplier.

Raw data were normalized with Genotyping console for SNP 6.0 and Chromosome Analysis Suite for Cytoscan HD.

Focal amplification of oncogenes was defined by log ratio>1.58 (6 copies per diploid genome) and maximum size <10 megabases. Biallelic inactivation of tumor suppressor genes was defined by homozygous deletion or truncating mutation associated with heterozygous deletion.

All PDX copy numbers were represented by the Circular Binary Segmentation algorithm as implemented in the DNAcopy package for R using a minimum width of 3, alpha less than 0.01 and up to 10,000 permutations.

The BRCAness signature was defined with large-scale state transitions, defined as chromosomal break between adjacent regions of at least 10Mb initially described by T. Popova