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Homozygous\n                    <jats:italic>MTAP<\/jats:italic>\n                    -deleted cell lines in culture show elevation of MTAP\u2019s substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes\n                    <jats:italic>MTAP<\/jats:italic>\n                    -deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept\u00a0has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that\u00a0MTA\u00a0secreted by\n                    <jats:italic>MTAP-<\/jats:italic>\n                    deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate that homozygous\n                    <jats:italic>MTAP<\/jats:italic>\n                    -deleted primary glioblastoma tumors\u00a0do not significantly accumulate MTA in vivo due to metabolism of MTA by MTAP-expressing stroma. These findings highlight metabolic discrepancies between in vitro models and primary human tumors that must be considered when developing strategies for precision therapies targeting glioblastoma with homozygous\n                    <jats:italic>MTAP<\/jats:italic>\n                    deletion.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-24240-3","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T06:03:11Z","timestamp":1625810591000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-1496","authenticated-orcid":false,"given":"Yasaman","family":"Barekatain","sequence":"first","affiliation":[]},{"given":"Jeffrey J.","family":"Ackroyd","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0837-5184","authenticated-orcid":false,"given":"Victoria C.","family":"Yan","sequence":"additional","affiliation":[]},{"given":"Sunada","family":"Khadka","sequence":"additional","affiliation":[]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Ko-Chien","family":"Chen","sequence":"additional","affiliation":[]},{"given":"Anton H.","family":"Poral","sequence":"additional","affiliation":[]},{"given":"Theresa","family":"Tran","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8786-2495","authenticated-orcid":false,"given":"Dimitra K.","family":"Georgiou","sequence":"additional","affiliation":[]},{"given":"Kenisha","family":"Arthur","sequence":"additional","affiliation":[]},{"given":"Yu-Hsi","family":"Lin","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3908-3731","authenticated-orcid":false,"given":"Nikunj","family":"Satani","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8484-5531","authenticated-orcid":false,"given":"Elliot S.","family":"Ballato","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-0733","authenticated-orcid":false,"given":"Eliot I.","family":"Behr","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1183-4548","authenticated-orcid":false,"given":"Ana C.","family":"deCarvalho","sequence":"additional","affiliation":[]},{"given":"Roel G. 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