@article{af459d29a9e847e88efd3323364ad13b,
title = "Chromosome-scale mega-haplotypes enable digital karyotyping of cancer aneuploidy",
abstract = "Genomic instability is a frequently occurring feature of cancer that involves large-scale structural alterations. These somatic changes in chromosome structure include duplication of entire chromosome arms and aneuploidy where chromosomes are duplicated beyond normal diploid content. However, the accurate determination of aneuploidy events in cancer genomes is a challenge. Recent advances in sequencing technology allow the characterization of haplotypes that extend megabases along the human genome using high molecular weight (HMW) DNA. For this study, we employed a library preparation method in which sequence reads have barcodes linked to single HMW DNA molecules. Barcodelinked reads are used to generate extended haplotypes on the order of megabases. We developed a method that leverages haplotypes to identify chromosomal segmental alterations in cancer and uses this information to join haplotypes together, thus extending the range of phased variants. With this approach, we identified mega-haplotypes that encompass entire chromosome arms. We characterized the chromosomal arm changes and aneuploidy events in a manner that offers similar information as a traditional karyotype but with the benefit of DNA sequence resolution. We applied this approach to characterize aneuploidy and chromosomal alterations from a series of primary colorectal cancers.",
author = "Bell, {John M.} and Lau, {Billy T.} and Greer, {Stephanie U.} and Christina Wood-Bouwens and Xia, {Li C.} and Connolly, {Ian D.} and Gephart, {Melanie H.} and Ji, {Hanlee P.}",
note = "Funding Information: National Institutes of Health (NIH) [NHGRI P01HG000205 to B.T.L., J.M.B., H.P.J.; NHGRI R01HG006137 (to L.C.X., H.P.J.); NCI R33CA174575 (to J.M.B., H.P.J.); NCI R21CA193046 (to I.D.C., M.H.G.)]; Stanford Cancer Institute Translational Research Award (to H.P.J., J.M.B.); American Cancer Society Research Scholar Grant [RSG-13–297-01-TBG] (to S.G., H.P.J); Doris Duke Charitable Foundation, Clayville Foundation, Seiler Foundation and Howard Hughes Medical Institute (to H.P.J.). Funding for open access charge: NIH. Conflict of interest statement. None declared. Funding Information: National Institutes of Health (NIH) [NHGRI P01HG000205 to B.T.L., J.M.B., H.P.J.; NHGRI R01HG006137 (to L.C.X., H.P.J.); NCI R33CA174575 (to J.M.B., H.P.J.); NCI R21CA193046 (to I.D.C., M.H.G.)]; Stanford Cancer Institute Translational Research Award (to H.P.J., J.M.B.); American Cancer Society Research Scholar Grant [RSG-13-297-01-TBG] (to S.G., H.P.J); Doris Duke Charitable Foundation, Clayville Foundation, Seiler Foundation and Howard Hughes Medical Institute (to H.P.J.). Funding for open access charge: NIH. Conflict of interest statement. None declared. Publisher Copyright: {\textcopyright} The Author(s) 2017.",
year = "2017",
month = nov,
day = "2",
doi = "10.1093/nar/gkx712",
language = "English (US)",
volume = "45",
journal = "Nucleic acids research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "19",
}
