Robust detection of oncometabolic aberrations by 1H–13C heteronuclear single quantum correlation in intact biological specimens
Magnetic resonance (MR) spectroscopy has potential to non-invasively detect metabolites of diagnostic significance for precision oncology. Yet, many metabolites have similar chemical shifts, yielding highly convoluted 1 H spectra of intact biological material and limiting diagnostic utility. Here, w...
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| Veröffentlicht in: | Communications biology 2020-06, Vol.3 (1), p.328-328, Article 328 |
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| creator | Barekatain, Yasaman Yan, Victoria C. Arthur, Kenisha Ackroyd, Jeffrey J. Khadka, Sunada De Groot, John Huse, Jason T. Muller, Florian L. |
| description | Magnetic resonance (MR) spectroscopy has potential to non-invasively detect metabolites of diagnostic significance for precision oncology. Yet, many metabolites have similar chemical shifts, yielding highly convoluted
1
H spectra of intact biological material and limiting diagnostic utility. Here, we show that hydrogen–carbon heteronuclear single quantum correlation (
1
H–
13
C HSQC) offers dramatic improvements in sensitivity compared to one-dimensional (1D)
13
C NMR and significant signal deconvolution compared to 1D
1
H spectra in intact biological settings. Using a standard NMR spectroscope with a cryoprobe but without specialized signal enhancing features such as magic angle spinning, metabolite extractions or
13
C-isotopic enrichment, we obtain well-resolved 2D
1
H–
13
C HSQC spectra in live cancer cells, in ex vivo freshly dissected xenografted tumors and resected primary tumors. This method can identify tumors with specific oncometabolite alterations such as
IDH
mutations by 2-hydroxyglutarate and
PGD
-deleted tumors by gluconate. Results suggest potential of
1
H–
13
C HSQC as a non-invasive diagnostic in precision oncology.
Barekatain et al. demonstrate that hydrogen–carbon heteronuclear single quantum correlation (HSQC) spectra, obtained using a standard NMR spectroscope, can detect tumours with specific oncometabolite alterations including
IDH1
mutant glioblastoma, suggesting the feasibility of this method as a diagnostic tool. |
| doi_str_mv | 10.1038/s42003-020-1055-5 |
| format | Article |
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1
H spectra of intact biological material and limiting diagnostic utility. Here, we show that hydrogen–carbon heteronuclear single quantum correlation (
1
H–
13
C HSQC) offers dramatic improvements in sensitivity compared to one-dimensional (1D)
13
C NMR and significant signal deconvolution compared to 1D
1
H spectra in intact biological settings. Using a standard NMR spectroscope with a cryoprobe but without specialized signal enhancing features such as magic angle spinning, metabolite extractions or
13
C-isotopic enrichment, we obtain well-resolved 2D
1
H–
13
C HSQC spectra in live cancer cells, in ex vivo freshly dissected xenografted tumors and resected primary tumors. This method can identify tumors with specific oncometabolite alterations such as
IDH
mutations by 2-hydroxyglutarate and
PGD
-deleted tumors by gluconate. Results suggest potential of
1
H–
13
C HSQC as a non-invasive diagnostic in precision oncology.
Barekatain et al. demonstrate that hydrogen–carbon heteronuclear single quantum correlation (HSQC) spectra, obtained using a standard NMR spectroscope, can detect tumours with specific oncometabolite alterations including
IDH1
mutant glioblastoma, suggesting the feasibility of this method as a diagnostic tool.</description><identifier>ISSN: 2399-3642</identifier><identifier>EISSN: 2399-3642</identifier><identifier>DOI: 10.1038/s42003-020-1055-5</identifier><identifier>PMID: 32587392</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>101/6 ; 13/106 ; 631/1647/320 ; 631/67/69 ; 64/60 ; 692/308/53/2421 ; 692/699/67/2327 ; Biology ; Biomedical and Life Sciences ; Glioblastoma ; Life Sciences ; Metabolites ; NMR ; Nuclear magnetic resonance ; Oncology ; Precision medicine ; Spectroscopy ; Spectrum analysis ; Tumors ; Xenografts</subject><ispartof>Communications biology, 2020-06, Vol.3 (1), p.328-328, Article 328</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2925-3935ebc888579b214285f7a70c3b0bfa314098ca101988b4ea8b49de3dcb58f93</citedby><cites>FETCH-LOGICAL-c2925-3935ebc888579b214285f7a70c3b0bfa314098ca101988b4ea8b49de3dcb58f93</cites><orcidid>0000-0001-7568-2948</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316726/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316726/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51554,53769,53771</link.rule.ids></links><search><creatorcontrib>Barekatain, Yasaman</creatorcontrib><creatorcontrib>Yan, Victoria C.</creatorcontrib><creatorcontrib>Arthur, Kenisha</creatorcontrib><creatorcontrib>Ackroyd, Jeffrey J.</creatorcontrib><creatorcontrib>Khadka, Sunada</creatorcontrib><creatorcontrib>De Groot, John</creatorcontrib><creatorcontrib>Huse, Jason T.</creatorcontrib><creatorcontrib>Muller, Florian L.</creatorcontrib><title>Robust detection of oncometabolic aberrations by 1H–13C heteronuclear single quantum correlation in intact biological specimens</title><title>Communications biology</title><addtitle>Commun Biol</addtitle><description>Magnetic resonance (MR) spectroscopy has potential to non-invasively detect metabolites of diagnostic significance for precision oncology. Yet, many metabolites have similar chemical shifts, yielding highly convoluted
1
H spectra of intact biological material and limiting diagnostic utility. Here, we show that hydrogen–carbon heteronuclear single quantum correlation (
1
H–
13
C HSQC) offers dramatic improvements in sensitivity compared to one-dimensional (1D)
13
C NMR and significant signal deconvolution compared to 1D
1
H spectra in intact biological settings. Using a standard NMR spectroscope with a cryoprobe but without specialized signal enhancing features such as magic angle spinning, metabolite extractions or
13
C-isotopic enrichment, we obtain well-resolved 2D
1
H–
13
C HSQC spectra in live cancer cells, in ex vivo freshly dissected xenografted tumors and resected primary tumors. This method can identify tumors with specific oncometabolite alterations such as
IDH
mutations by 2-hydroxyglutarate and
PGD
-deleted tumors by gluconate. Results suggest potential of
1
H–
13
C HSQC as a non-invasive diagnostic in precision oncology.
Barekatain et al. demonstrate that hydrogen–carbon heteronuclear single quantum correlation (HSQC) spectra, obtained using a standard NMR spectroscope, can detect tumours with specific oncometabolite alterations including
IDH1
mutant glioblastoma, suggesting the feasibility of this method as a diagnostic tool.</description><subject>101/6</subject><subject>13/106</subject><subject>631/1647/320</subject><subject>631/67/69</subject><subject>64/60</subject><subject>692/308/53/2421</subject><subject>692/699/67/2327</subject><subject>Biology</subject><subject>Biomedical and Life Sciences</subject><subject>Glioblastoma</subject><subject>Life Sciences</subject><subject>Metabolites</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Oncology</subject><subject>Precision medicine</subject><subject>Spectroscopy</subject><subject>Spectrum analysis</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>2399-3642</issn><issn>2399-3642</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kd1qFTEUhYMobWn7AL0LeOPNaH4mM8mNIAe1QkGQeh2SnD2nKZnkNMkIvavP4Bv6JGY8xT8QQhLY31o7OwuhC0peUsLlq9IzQnhHGOkoEaITT9AJ40p1fOjZ0z_ux-i8lFtCCFVKDbw_QsecCTlyxU7Q10_JLqXiLVRw1aeI04RTdGmGamwK3mFjIWez1gq295hefn_4RvkG3zRJTnFxAUzGxcddAHy3mFiXGbuUM4SfKuzXVY2r2PoU0s47E3DZg_MzxHKGnk0mFDh_PE_R53dvrzeX3dXH9x82b646xxQTHVdcgHVSSjEqy2jPpJhGMxLHLbGT4bQnSjpD25hS2h5M29QW-NZZISfFT9Hrg-9-sTNsHcSaTdD77GeT73UyXv9dif5G79IXPXI6jGxoBi8eDXK6W6BUPfviIAQTIS1Fs55KytuPr72e_4PepiXHNt5KjXQYpOgbRQ-Uy6mUDNOvx1Ci14z1IWPdMtZrxlo0DTtoSmPjDvJv5_-LfgBvvasQ</recordid><startdate>20200625</startdate><enddate>20200625</enddate><creator>Barekatain, Yasaman</creator><creator>Yan, Victoria C.</creator><creator>Arthur, Kenisha</creator><creator>Ackroyd, Jeffrey J.</creator><creator>Khadka, Sunada</creator><creator>De Groot, John</creator><creator>Huse, Jason T.</creator><creator>Muller, Florian L.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7568-2948</orcidid></search><sort><creationdate>20200625</creationdate><title>Robust detection of oncometabolic aberrations by 1H–13C heteronuclear single quantum correlation in intact biological specimens</title><author>Barekatain, Yasaman ; 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Yet, many metabolites have similar chemical shifts, yielding highly convoluted
1
H spectra of intact biological material and limiting diagnostic utility. Here, we show that hydrogen–carbon heteronuclear single quantum correlation (
1
H–
13
C HSQC) offers dramatic improvements in sensitivity compared to one-dimensional (1D)
13
C NMR and significant signal deconvolution compared to 1D
1
H spectra in intact biological settings. Using a standard NMR spectroscope with a cryoprobe but without specialized signal enhancing features such as magic angle spinning, metabolite extractions or
13
C-isotopic enrichment, we obtain well-resolved 2D
1
H–
13
C HSQC spectra in live cancer cells, in ex vivo freshly dissected xenografted tumors and resected primary tumors. This method can identify tumors with specific oncometabolite alterations such as
IDH
mutations by 2-hydroxyglutarate and
PGD
-deleted tumors by gluconate. Results suggest potential of
1
H–
13
C HSQC as a non-invasive diagnostic in precision oncology.
Barekatain et al. demonstrate that hydrogen–carbon heteronuclear single quantum correlation (HSQC) spectra, obtained using a standard NMR spectroscope, can detect tumours with specific oncometabolite alterations including
IDH1
mutant glioblastoma, suggesting the feasibility of this method as a diagnostic tool.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32587392</pmid><doi>10.1038/s42003-020-1055-5</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-7568-2948</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 101/6 13/106 631/1647/320 631/67/69 64/60 692/308/53/2421 692/699/67/2327 Biology Biomedical and Life Sciences Glioblastoma Life Sciences Metabolites NMR Nuclear magnetic resonance Oncology Precision medicine Spectroscopy Spectrum analysis Tumors Xenografts |
| title | Robust detection of oncometabolic aberrations by 1H–13C heteronuclear single quantum correlation in intact biological specimens |
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