The online version of this article (https://doi.org/10.1186/s12943-018-0876-z) contains supplementary material, which is available to authorized users.
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are the most heritable endocrine tumors. Genetic testing for 12 driver susceptibility genes is recommended in all PCC and PGL cases. However, detection of somatic mutations in PCC and PGL remains unrealizable for genetic diagnosis and preoperative assessment. We compared the serum exosomal DNA and tumor tissue DNA from patients or mice with PCC or PGL and found double-stranded DNA (dsDNA) fragments in the circulating exosomes of patients with PCC or PGL. Exosomal dsDNA shared the same mutations in the susceptibility genes with that of the parent tumor cells. Moreover, our research showed that serum-derived exosomal dsDNA in PCC and PGL was highly consistent with the paired tumor genome. Our findings provide the first definitive evidence of the presence of exosomal dsDNA that can be used as a noninvasive genetic marker in one of the most effective somatic mutation screens for the diagnosis and preoperative assessment of PCCs and PGLs.
Additional file 1: Methods and materials used during this study. (DOCX 45 kb)12943_2018_876_MOESM1_ESM.docx
Additional file 2: Table S1. Mutations in nude mice. (DOCX 82 kb)12943_2018_876_MOESM2_ESM.docx
Additional file 3: Table S2. Clinical and genetic characteristic of the PCCs/PGLs patients. (DOCX 21 kb)12943_2018_876_MOESM3_ESM.docx
Additional file 4: Table S3. Common SNP in exo-DNA I and genomic DNA of PC12 cells. (XLS 1157 kb)12943_2018_876_MOESM4_ESM.xls
Additional file 5: Table S4. Common SNP of susceptibility genes in exo-DNA III and the parental tumor cells from patient 13. Table S5. Common SNP of susceptibility genes in exo-DNA III and the parental tumor celsl from patient 14. Table S6. Common SNP of susceptibility genes in exo-DNA III and the parental tumor cells from patient 15. Table S7. Common SNP counts in three of the patients. (ZIP 184 kb)12943_2018_876_MOESM5_ESM.zip
Lenders JWM, Eisenhofer G. Update on modern Management of Pheochromocytoma and Paraganglioma. Endocrinol Metab. 2017;32:152–61. CrossRef
Brito JP, et al. Testing for germline mutations in sporadic pheochromocytoma/paraganglioma: a systematic review. Clin Endocrinol. 2015;82:338–45. CrossRef
- Exosomal double-stranded DNA as a biomarker for the diagnosis and preoperative assessment of pheochromocytoma and paraganglioma
- BioMed Central
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