Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm.
Title | Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Stenzinger, A., Endris V., Pfarr N., Andrulis M., Jöhrens K., Klauschen F., Siebolts U., Wolf T., Koch P-S., Schulz M., Hartschuh W., Goerdt S., Lennerz J. K., Wickenhauser C., Klapper W., Anagnostopoulos I., & Weichert W. |
Journal | Oncotarget |
Volume | 5 |
Issue | 15 |
Pagination | 6404-13 |
Date Published | 2014 Aug 15 |
ISSN | 1949-2553 |
Keywords | Aged, Aged, 80 and over, Blast Crisis, Dendritic Cells, DNA Mutational Analysis, Female, Hematologic Neoplasms, Humans, Male, Middle Aged, Mutation, Plasmacytoma, Skin Neoplasms |
Abstract | Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1%), as well as in VHL, BRAF, MLH1, TP53 and RET1 (3% each). Moreover, NRAS-, KRAS- and ATM-mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored. |
DOI | 10.18632/oncotarget.2223 |
Alternate Journal | Oncotarget |
PubMed ID | 25115387 |
PubMed Central ID | PMC4171639 |