A somatic reference standard for cancer genome sequencing.
Large-scale multiplexed identification of somatic alterations in cancer has become feasible with next generation sequencing (NGS). However, calibration of NGS somatic analysis tools has been hampered by a lack of tumor/normal reference standards. We thus performed paired PCR-free whole genome sequencing of a matched metastatic melanoma cell line (COLO829) and normal across three lineages and across separate institutions, with independent library preparations, sequencing, and analysis. We generated mean mapped coverages of 99X for COLO829 and 103X for the paired normal across three institutions. Results were combined with previously generated data allowing for comparison to a fourth lineage on earlier NGS technology. Aggregate variant detection led to the identification of consensus variants, including key events that represent hallmark mutation types including amplified BRAF V600E, a CDK2NA small deletion, a 12 kb PTEN deletion, and a dinucleotide TERT promoter substitution. Overall, common events include >35,000 point mutations, 446 small insertion/deletions, and >6,000 genes affected by copy number changes. We present this reference to the community as an initial standard for enabling quantitative evaluation of somatic mutation pipelines across institutions.
Translational Genomics Research Institute, Phoenix, Arizona, USA.
David W
DW
Craig
Translational Genomics Research Institute, Phoenix, Arizona, USA.
Sara
S
Nasser
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, BC, V5Z 4S6, Canada.
Richard
R
Corbett
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, BC, V5Z 4S6, Canada.
Simon K
SK
Chan
Illumina Cambridge, Ltd., Saffron Walden, UK.
Lisa
L
Murray
Translational Genomics Research Institute, Phoenix, Arizona, USA.
Christophe
C
Legendre
Translational Genomics Research Institute, Phoenix, Arizona, USA.
Waibhav
W
Tembe
Translational Genomics Research Institute, Phoenix, Arizona, USA.
Jonathan
J
Adkins
Illumina, Inc., San Diego, California, USA.
Nancy
N
Kim
Translational Genomics Research Institute, Phoenix, Arizona, USA.
Shukmei
S
Wong
Translational Genomics Research Institute, Phoenix, Arizona, USA.
Angela
A
Baker
Translational Genomics Research Institute, Phoenix, Arizona, USA.
Daniel
D
Enriquez
Illumina, Inc., San Diego, California, USA.
Stephanie
S
Pond
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, BC, V5Z 4S6, Canada.
Erin
E
Pleasance
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, BC, V5Z 4S6, Canada.
Andrew J
AJ
Mungall
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, BC, V5Z 4S6, Canada.
Richard A
RA
Moore
Illumina, Inc., San Diego, California, USA.
Timothy
T
McDaniel
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, BC, V5Z 4S6, Canada.
Yussanne
Y
Ma
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, BC, V5Z 4S6, Canada.
Steven J M
SJ
Jones
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency (BCCA), Vancouver, BC, V5Z 4S6, Canada.
Marco A
MA
Marra
Translational Genomics Research Institute, Phoenix, Arizona, USA.
John D
JD
Carpten
Translational Genomics Research Institute, Phoenix, Arizona, USA.
Winnie S
WS
Liang
D045744:Cell Line, Tumor; D066264:Datasets as Topic; D014644:Genetic Variation; D016678:Genome; D023281:Genomics / Q000379:methods* / Q000592:standards*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015201:Meta-Analysis as Topic; D009369:Neoplasms / Q000235:genetics*; D012015:Reference Standards