Next generation mapping reveals novel large genomic rearrangements in prostate cancer

dc.contributor.authorJaratlerdsiri, Weerachai
dc.contributor.authorChan, Eva K.F.
dc.contributor.authorPetersen, Desiree C.
dc.contributor.authorYang, Claire
dc.contributor.authorCroucher, Peter I.
dc.contributor.authorBornman, Maria S. (Riana)
dc.contributor.authorSheth, Palak
dc.contributor.authorHayes, Vanessa M.
dc.date.accessioned2018-01-31T09:39:56Z
dc.date.available2018-01-31T09:39:56Z
dc.date.issued2017-03-01
dc.description.abstractComplex genomic rearrangements are common molecular events driving prostate carcinogenesis. Clinical significance, however, has yet to be fully elucidated. Detecting the full range and subtypes of large structural variants (SVs), greater than one kilobase in length, is challenging using clinically feasible next generation sequencing (NGS) technologies. Next generation mapping (NGM) is a new technology that allows for the interrogation of megabase length DNA molecules outside the detection range of single-base resolution NGS. In this study, we sought to determine the feasibility of using the Irys (Bionano Genomics Inc.) nanochannel NGM technology to generate whole genome maps of a primary prostate tumor and matched blood from a Gleason score 7 (4 + 3), ETS-fusion negative prostate cancer patient. With an effective mapped coverage of 35X and sequence coverage of 60X, and an estimated 43% tumor purity, we identified 85 large somatic structural rearrangements and 6,172 smaller somatic variants, respectively. The vast majority of the large SVs (89%), of which 73% are insertions, were not detectable ab initio using high-coverage short-read NGS. However, guided manual inspection of single NGS reads and de novo assembled scaffolds of NGM-derived candidate regions allowed for confirmation of 94% of these large SVs, with over a third impacting genes with oncogenic potential. From this single-patient study, the first cancer study to integrate NGS and NGM data, we hypothesise that there exists a novel spectrum of large genomic rearrangements in prostate cancer, that these large genomic rearrangements are likely early events in tumorigenesis, and they have potential to enhance taxonomy.en_ZA
dc.description.departmentSchool of Health Systems and Public Health (SHSPH)en_ZA
dc.description.librarianam2018en_ZA
dc.description.sponsorshipThis work was supported by Movember Australia and the Prostate Cancer Foundation Australia (PCFA) as part of the Movember Revolutionary Team Award (MRTA) to the Garvan Institute of Medical Research program on prostate cancer bone metastasis (ProMis to P.I.C. and V.M.H.) dedicated to establishing NGM for clinically relevant prostate cancer, and the Australian Prostate Cancer Research Centre NSW (APCRC-NSW). Participant recruitment and sampling was supported by the Cancer Association of South Africa (CANSA to M.S.R.B and V.M.H.). W.J. is supported by APCRC-NSW, E.K.F.C. and D.C.P. are partly supported by ProMis, P.I.C. is supported by Mrs Janice Gibson and the Ernest Heine Family Foundation, Australia, and V.M.H. is supported by the University of Sydney Foundation and Petre Foundation, Australia.en_ZA
dc.description.uriwww.impactjournals.com/oncotargeten_ZA
dc.identifier.citationJaratlerdsiri, W.,Chan, E.K.F., Petersen, D.C. et al. 2017, 'Next generation mapping reveals novel large genomic rearrangements in prostate cancer', Oncotarget, vol. 8, no. 14, pp. 23588-23602.en_ZA
dc.identifier.issn1949-2553 (online)
dc.identifier.urihttp://hdl.handle.net/2263/63822
dc.language.isoenen_ZA
dc.publisherImpact Journalsen_ZA
dc.rightsCopyright: [Jaratlerdsiri] et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License.en_ZA
dc.subjectProstate canceren_ZA
dc.subjectStructural genomic rearrangementsen_ZA
dc.subjectNext generation mapping (NGM)en_ZA
dc.subjectStructural variant (SV)en_ZA
dc.subjectNext generation sequencing (NGS)en_ZA
dc.titleNext generation mapping reveals novel large genomic rearrangements in prostate canceren_ZA
dc.typeArticleen_ZA

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