PMID- 31491926
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 11
IP  - 9
DP  - 2019 Sep 5
TI  - RNA-Based Detection of Gene Fusions in Formalin-Fixed and Paraffin-Embedded Solid 
      Cancer Samples.
LID - 10.3390/cancers11091309 [doi]
LID - 1309
AB  - Oncogenic gene fusions are important drivers in many cancer types, including 
      carcinomas, with diagnostic and therapeutic implications. Hence, sensitive and 
      rapid methods for parallel profiling in formalin-fixed and paraffin-embedded 
      (FFPE) specimens are needed. In this study we analyzed gene fusions in a cohort 
      of 517 cases where standard treatment options were exhausted. To this end the 
      Archer((R)) DX Solid tumor panel (AMP; 285 cases) and the Oncomine Comprehensive 
      Assay v3 (OCA; 232 cases) were employed. Findings were validated by Sanger 
      sequencing, fluorescence in situ hybridization (FISH) or immunohistochemistry. 
      Both assays demonstrated minimal dropout rates (AMP: 2.4%; n = 7/292, OCA: 2.1%; 
      n = 5/237) with turnaround times of 6-9 working days (median, OCA and AMP, 
      respectively). Hands-on-time for library preparation was 6 h (AMP) and 2 h (OCA). 
      We detected n = 40 fusion-positive cases (7.7%) with TMPRSS2::ERG in prostate 
      cancer being most prevalent (n = 9/40; 22.5%), followed by other gene fusions 
      identified in cancers of unknown primary (n = 6/40; 15.0%), adenoid cystic 
      carcinoma (n = 7/40; 17.5%), and pancreatic cancer (n = 7/40; 17.5%). Our results 
      demonstrate that targeted RNA-sequencing of FFPE samples is feasible, and a 
      well-suited approach for the detection of gene fusions in a routine clinical 
      setting.
FAU - Kirchner, Martina
AU  - Kirchner M
AUID- ORCID: 0000-0003-4426-2400
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Neumann, Olaf
AU  - Neumann O
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Volckmar, Anna-Lena
AU  - Volckmar AL
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Stogbauer, Fabian
AU  - Stogbauer F
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Allgauer, Michael
AU  - Allgauer M
AUID- ORCID: 0000-0003-4518-7887
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Kazdal, Daniel
AU  - Kazdal D
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Budczies, Jan
AU  - Budczies J
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
AD  - German Cancer Consortium (DKTK), 69120 Heidelberg partner sites, Germany.
FAU - Rempel, Eugen
AU  - Rempel E
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Brandt, Regine
AU  - Brandt R
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Talla, Suranand Babu
AU  - Talla SB
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - von Winterfeld, Moritz
AU  - von Winterfeld M
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Leichsenring, Jonas
AU  - Leichsenring J
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Bochtler, Tilmann
AU  - Bochtler T
AD  - Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research 
      Center (DKFZ), 69120 Heidelberg, Germany.
AD  - Department of Internal Medicine V, University Hospital Heidelberg, 69120 
      Heidelberg, Germany.
FAU - Kramer, Alwin
AU  - Kramer A
AD  - Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research 
      Center (DKFZ), 69120 Heidelberg, Germany.
AD  - Department of Internal Medicine V, University Hospital Heidelberg, 69120 
      Heidelberg, Germany.
FAU - Springfeld, Christoph
AU  - Springfeld C
AD  - Department of Internal Medicine VI, University Hospital Heidelberg, 69120 
      Heidelberg, Germany.
AD  - National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany.
FAU - Schirmacher, Peter
AU  - Schirmacher P
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
AD  - German Cancer Consortium (DKTK), 69120 Heidelberg partner sites, Germany.
FAU - Penzel, Roland
AU  - Penzel R
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Endris, Volker
AU  - Endris V
AUID- ORCID: 0000-0003-2550-3563
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany.
FAU - Stenzinger, Albrecht
AU  - Stenzinger A
AD  - Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, 
      Germany. albrecht.stenzinger@med.uni-heidelberg.de.
AD  - German Cancer Consortium (DKTK), 69120 Heidelberg partner sites, Germany. 
      albrecht.stenzinger@med.uni-heidelberg.de.
LA  - eng
PT  - Journal Article
DEP - 20190905
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC6769558
OTO - NOTNLM
OT  - NGS
OT  - carcinoma
OT  - gene fusion
OT  - solid tumor
OT  - targeted therapy
COIS- Albrecht Stenzinger: Advisory board honoraria from Bayer, Novartis, BMS, 
      AstraZeneca, ThermoFisher, Illumina; speaker s honoraria from Takeda, Roche, BMS, 
      Illumina, AstraZeneca, Novartis, ThermoFisher, Bayer, MSD and research funding 
      from Chugai and BMS. Volker Endris: Advisory board honoraria from ThermoFisher; 
      Speaker s honoraria from AstraZeneca. Peter Schirmacher: Advisory board honoraria 
      from Pfizer, Roche, Novartis and AstraZeneca; speaker s honoraria and research 
      funding from Roche, AstraZeneca and Novartis. Anna-Lena Volckmar: Funding from 
      AstraZeneca for a talk. Alwin Kramer: Reimbursement of study-related traveling 
      and molecular tumor board work by Roche. Tilman Bochtler: Reimbursement of 
      study-related traveling and molecular tumor board work by Roche. The sponsors had 
      no role in the design, execution, interpretation, or writing of the study. M.K., 
      O.N., M.A., J.B., E.R., R.P., R.B., D.K., S.B.T., L.J., F.S., M.v.W. and C.S. 
      declare no conflict of interest.
EDAT- 2019/09/08 06:00
MHDA- 2019/09/08 06:01
PMCR- 2019/09/05
CRDT- 2019/09/08 06:00
PHST- 2019/08/13 00:00 [received]
PHST- 2019/08/27 00:00 [accepted]
PHST- 2019/09/08 06:00 [entrez]
PHST- 2019/09/08 06:00 [pubmed]
PHST- 2019/09/08 06:01 [medline]
PHST- 2019/09/05 00:00 [pmc-release]
AID - cancers11091309 [pii]
AID - cancers-11-01309 [pii]
AID - 10.3390/cancers11091309 [doi]
PST - epublish
SO  - Cancers (Basel). 2019 Sep 5;11(9):1309. doi: 10.3390/cancers11091309.