A map of mobile DNA insertions in the NCI-60 human cancer cell panel.
BACKGROUND
The National Cancer Institute-60 (NCI-60) cell lines are among the most widely used models of human cancer. They provide a platform to integrate DNA sequence information, epigenetic data, RNA and protein expression, and pharmacologic susceptibilities in studies of cancer cell biology. Genome-wide studies of the complete panel have included exome sequencing, karyotyping, and copy number analyses but have not targeted repetitive sequences. Interspersed repeats derived from mobile DNAs are a significant source of heritable genetic variation, and insertions of active elements can occur somatically in malignancy.


METHODS
We used Transposon Insertion Profiling by microarray (TIP-chip) to map Long INterspersed Element-1 (LINE-1, L1) andAluShort INterspersed Element (SINE) insertions in cancer genes in NCI-60 cells. We focused this discovery effort on annotated Cancer Gene Index loci.


RESULTS
We catalogued a total of 749 and 2,100 loci corresponding to candidate LINE-1 andAluinsertion sites, respectively. As expected, these numbers encompass previously known insertions, polymorphisms shared in unrelated tumor cell lines, as well as unique, potentially tumor-specific insertions. We also conducted association analyses relating individual insertions to a variety of cellular phenotypes.


CONCLUSIONS
These data provide a resource for investigators with interests in specific cancer gene loci or mobile element insertion effects more broadly. Our data underscore that significant genetic variation in cancer genomes is owed to LINE-1 andAluretrotransposons. Our findings also indicate that as large numbers of cancer genomes become available, it will be possible to associate individual transposable element insertion variants with molecular and phenotypic features of these malignancies.
Department of Dermatology, Johns Hopkins University School of Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA.
John G
JG
Zampella
Department of Pathology, Johns Hopkins University School of Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA.
Nemanja
N
Rodić
Department of Pathology, Johns Hopkins University School of Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA.
Wan Rou
WR
Yang
McKusick-Nathans Institute of Genetic Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA.
Cheng Ran Lisa
CR
Huang
McKusick-Nathans Institute of Genetic Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA.
Jane
J
Welch
McKusick-Nathans Institute of Genetic Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA.
Veena P
VP
Gnanakkan
Department of Pathology, Johns Hopkins University School of Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA.
Toby C
TC
Cornish
McKusick-Nathans Institute of Genetic Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA ; High Throughput (HiT) Biology Center, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA ; Present address: Institute for Systems Genetics, NYU Langone University School of Medicine, New York, NY 10016 USA.
Jef D
JD
Boeke
Department of Pathology, Johns Hopkins University School of Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA ; McKusick-Nathans Institute of Genetic Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA ; High Throughput (HiT) Biology Center, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA ; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 733 North Broadway, Miller Research Building Room 469, Baltimore, MD 21205 USA.
Kathleen H
KH
Burns