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J Neurooncol. 2018 Nov;140(2):269-279. doi: 10.1007/s11060-018-2978-2. Epub 2018 Aug 20.

Rapid discrimination of pediatric brain tumors by mass spectrometry imaging.

Author information

1
Department of Neurosurgery, Brigham and Woman's Hospital, Harvard Medical School, 60 Fenwood Road, 8016-J, Boston, MA, 02115, USA.
2
Program in Chemical Biology, Harvard University, Cambridge, MA, USA.
3
Therapeutics Graduate Program, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.
4
Winship Cancer Institute, Emory University School of Medicine, 1365C Clifton Road, Suite C5086, Atlanta, GA, 30322, USA.
5
Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
6
Departments of Chemistry and Pharm. Sci., Barnett Institute, Northeastern University, Boston, MA, USA.
7
Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
8
Department of Pathology and Laboratory Medicine, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
9
Department of Pathology, Brigham and Woman's Hospital, Harvard Medical School, Boston, MA, USA.
10
Department of Neurology, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
11
Department of Neurosurgery, Brigham and Woman's Hospital, Harvard Medical School, 60 Fenwood Road, 8016-J, Boston, MA, 02115, USA. Nathalie_Agar@dfci.harvard.edu.
12
Program in Chemical Biology, Harvard University, Cambridge, MA, USA. Nathalie_Agar@dfci.harvard.edu.
13
Therapeutics Graduate Program, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA. Nathalie_Agar@dfci.harvard.edu.
14
Department of Neurology, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA. Nathalie_Agar@dfci.harvard.edu.
15
Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Nathalie_Agar@dfci.harvard.edu.
16
Winship Cancer Institute, Emory University School of Medicine, 1365C Clifton Road, Suite C5086, Atlanta, GA, 30322, USA. soma.sengupta@emory.edu.
17
Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA. soma.sengupta@emory.edu.
18
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA. soma.sengupta@emory.edu.
19
Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA. soma.sengupta@emory.edu.

Abstract

PURPOSE:

Medulloblastoma, the most common primary pediatric malignant brain tumor, originates in the posterior fossa of the brain. Pineoblastoma, which originates within the pineal gland, is a rarer malignancy that also presents in the pediatric population. Medulloblastoma and pineoblastoma exhibit overlapping clinical features and have similar histopathological characteristics. Histopathological similarities confound rapid diagnoses of these two tumor types. We have conducted a pilot feasibility study analyzing the molecular profile of archived frozen human tumor specimens using mass spectrometry imaging (MSI) to identify potential biomarkers capable of classifying and distinguishing between medulloblastoma and pineoblastoma.

METHODS:

We performed matrix-assisted laser desorption ionization Fourier transform ion cyclotron resonance mass spectrometry imaging on eight medulloblastoma biopsy specimens and three pineoblastoma biopsy specimens. Multivariate statistical analyses were performed on the MSI dataset to generate classifiers that distinguish the two tumor types. Lastly, the molecules that were discriminative of tumor type were queried against the Lipid Maps database and identified.

RESULTS:

In this pilot study we show that medulloblastoma and pineoblastoma can be discriminated using molecular profiles determined by MSI. The highest-ranking discriminating classifiers of medulloblastoma and pineoblastoma were glycerophosphoglycerols and sphingolipids, respectively.

CONCLUSION:

We demonstrate proof-of-concept that medulloblastoma and pineoblastoma can be rapidly distinguished by using MSI lipid profiles. We identified biomarker candidates capable of distinguishing these two histopathologically similar tumor types. This work expands the current molecular knowledge of medulloblastoma and pineoblastoma by characterizing their lipidomic profiles, which may be useful for developing novel diagnostic, prognostic and therapeutic strategies.

KEYWORDS:

Biomarkers; Brain tumors; Lipids; Mass spectrometry imaging; Medulloblastoma; Pineoblastoma

PMID:
30128689
PMCID:
PMC6244779
DOI:
10.1007/s11060-018-2978-2
[Indexed for MEDLINE]
Free PMC Article

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