Proteogenomic Analysis of Protein Sequence Alterations in Breast Cancer Cells

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dc.contributor.authorLazar, Iuliana M.en
dc.contributor.authorKarcini, Arbaen
dc.contributor.authorAhuja, Shreyaen
dc.contributor.authorEstrada-Palma, Carlyen
dc.contributor.departmentBiochemistryen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentVirginia Tech Carilion School of Medicineen
dc.date.accessioned2019-11-06T18:38:07Zen
dc.date.available2019-11-06T18:38:07Zen
dc.date.issued2019-07-18en
dc.description.abstractCancer evolves as a result of an accumulation of mutations and chromosomal aberrations. Developments in sequencing technologies have enabled the discovery and cataloguing of millions of such mutations. The identification of protein-level alterations, typically by using reversed-phase protein arrays or mass spectrometry, has lagged, however, behind gene and transcript-level observations. In this study, we report the use of mass spectrometry for detecting the presence of mutations-missense, indels and frame shifts-in MCF7 and SKBR3 breast cancer, and non-tumorigenic MCF10A cells. The mutations were identified by expanding the database search process of raw mass spectrometry files by including an in-house built database of mutated peptides (XMAn-v1) that complemented a minimally redundant, canonical database of Homo sapiens proteins. The work resulted in the identification of nearly 300 mutated peptide sequences, of which ~50 were characterized by quality tandem mass spectra. We describe the criteria that were used to select the mutated peptide sequences, evaluate the parameters that characterized these peptides, and assess the artifacts that could have led to false peptide identifications. Further, we discuss the functional domains and biological processes that may be impacted by the observed peptide alterations, and how protein-level detection can support the efforts of identifying cancer driving mutations and genes. Mass spectrometry data are available via ProteomeXchange with identifier PXD014458.en
dc.description.sponsorshipThis work was supported by an award from NIGMS (1R01GM121920–01A1) to IML.en
dc.format.extent13 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-019-46897-zen
dc.identifier.urihttp://hdl.handle.net/10919/95313en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherNature Researchen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleProteogenomic Analysis of Protein Sequence Alterations in Breast Cancer Cellsen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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