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 

GENE LIST
ARID1A MLL3 AKT1 PTPN11 PIK3CA
SLC4A5 FAT1 AKT2 RAD51B PIK3R1
RB1 APC AKT3 RAD51C POLE
STX2 ARID2 ALK RET PPP2R1A
NBPF1 SLC39A6 ATM ROS1 PTEN
SMARCA4 ARHGAP35 BRCA1 STK11 MET
BRAF SMAD4 BRCA2 TP53 MTOR
CDKN2A CTNNB1 DDR2 TSC1 IDH2
RBM10 CDK12 EGFR TSC2 KDR
RIT1 MBD1 ESR1 VHL MAP2K4
U2AF1 FBXO16 HER2/Erbb2 FRFR4 MAP3K1
H3F3A PBLD HER3/Erbb3 HRAS KIT
MEK1 ZNF774 HER4/Erbb4 IDH1 KRAS
FGFR1 NRAS FBXW7 PALB2 MAP2K1
FGFR2 CDKN1B NF1 PDGFRA MAP2K2
NFE2L2 KEAP1 FGFR3    

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