Whole Genome Sequencing Informs Therapeutic Selection for Pancreatic Cancer

·发布 2015年2月27日 ·更新 2015年3月8日

100

样本数

100

实验数

芯片平台

相关文献

实验描述

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole genome sequencing and CNV analysis of 100 pancreatic ductal adenocarcinomas. Chromosomal rearrangements leading to gene disruption were frequent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A, ROBO2) and novel candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation classified PDAC into 4 subtypes with potential clinical utility: stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3, and PIK3CA), but at low individual frequency. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2, PALB2 or RPA1), and a mutational signature of DNA damage repair deficiency. This subgroup was associated with response to platinum-based therapy and defines candidate biomarkers of therapeutic responsiveness. DNA was assayed using Illumina SNP BeadChips as per manufacturer’s instructions (Illumina, San Diego CA) (HumanOmni1-Quad or HumanOmni2.5-8 BeadChips). SNP arrays were scanned and data was processed using the Genotyping module (v1.8.4) in Genomestudio v2010.3 (Illumina, San Diego CA) to calculate B-allele frequencies (BAF) and logR values. GenoCN4 and GAP5 were used to call somatic regions of copy number change – gain, loss or copy neutral LOH. Recurrent regions of copy number change were determined and genes within these regions were extracted using ENSEMBL v70 annotations. Significant regions of gain and loss were identified by GISTIC6.

参考文献

Whole genomes redefine the mutational landscape of pancreatic cancer.

Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grï¿½tzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA, Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM

PMID: 25719666

芯片平台

A-GEOD-16104

Illumina HumanOmni2.5-8 BeadChip（70 例）

A-GEOD-8882

Illumina HumanOmni1-Quad BeadChip（30 例）

样本属性

cell type

Cell Line Derived From Tumour, Cell Line Derived From Xenograft, Primary Tumour

disease

Pancreatic Adenocarcinoma

organism

Homo sapiens

实验信息

登记号

E-GEOD-61502

GEO 编号

GSE61502

实验类型

comparative genomic hybridization by array

物种

Homo sapiens

发布日期

2015年2月27日

更新日期

2015年3月8日

提交者

Conrad Leonard、 Anirban Maitra、 Nicole Cloonan、 Darrin Taylor、 Suzanne Manning、 Kelly Quek、 Senel Idrisoglu、 Massimo Falconi、 Katia Nones、 Giuseppe Zamboni、 Jaswinder S Samra、 Vincenzo Corbo、 Ralph H Hruban、 James G Kench、 Nigel B Jamieson、 Mark J Cowley、 Peter J Wilson、 Mark Pinese、 Neil D Merrett、 Timothy J Bruxner、 Ehsan Nourbakhsh、 Alan Robertson、 Marina Pajic、 Ilse Rooman、 Richard A Morgan、 Muhammad Fudlullah、 Matthew Anderson、 Andrew V Biankin、 James R Eshleman、 Andrew P Barbour、 David K Chang、 Robert L Sutherland、 Shivangi Wani、 Aldo Scarpa、 Karin S Kassahn、 Amber L Johns、 Christian Pilarsky、 Christopher J Scarlett、 Michael Quinn、 Nikolajs Zeps、 David Miller、 Stephen Kazakoff、 John V Pearson、 Scott Wood、 J L Fink、 Marc D Jones、 Jeremy Humphris、 Amanda Mawson、 Claudio Bassi、 Jianmin Wu、 Jessica A Lovell、 Ivon Harliwong、 Robert Grützmann、 Margaret A Tempero、 Qinying Xu、 Nam Q Nguyen、 Sean M Grimmond、 Nick Waddell、 Giampaolo Tortora、 Emily S Humphrey、 Anthony J Gill、 Nicola Waddell、 Craig Nourse、 Emily K Colvin、 Elizabeth A Musgrove、 Krishna Epari、 Angelika N Christ、 Janet S Graham、 Ann-Marie Patch、 Oliver Holmes、 Rita T Lawlor、 Christopher Toon、 Peter Bailey、 Lorraine A Chantrill、 Andreia V Pinho、 Felicity Newell、 Adnan M Nagrial、 Sarah Song、 Christopher L Wolfgang、 Angela Chou、 Katia Nones、 Emma Markham、 Christine A Iacobuzio-Donahue

外部链接

ArrayExpress 原始页 NCBI GEO：GSE61502

分析服务

Whole Genome Sequencing Informs Therapeutic Selection for Pancreatic Cancer

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