PMID- 29025587
OWN - NLM
STAT- MEDLINE
DCOM- 20171030
LR  - 20171030
IS  - 2210-7762 (Print)
VI  - 216-217
DP  - 2017 Oct
TI  - Addition of chromosomal microarray and next generation sequencing to FISH and 
      classical cytogenetics enhances genomic profiling of myeloid malignancies.
PG  - 128-141
LID - S2210-7762(17)30324-1 [pii]
LID - 10.1016/j.cancergen.2017.07.010 [doi]
AB  - Comprehensive genetic profiling is increasingly important for the clinical workup 
      of hematologic tumors, as specific alterations are now linked to diagnostic 
      characterization, prognostic stratification and therapy selection. To 
      characterize relevant genetic and genomic alterations in myeloid malignancies 
      maximally, we utilized a comprehensive strategy spanning fluorescence in situ 
      hybridization (FISH), classical karyotyping, Chromosomal Microarray (CMA) for 
      detection of copy number variants (CNVs) and Next generation Sequencing (NGS) 
      analysis. In our cohort of 569 patients spanning the myeloid spectrum, NGS and 
      CMA testing frequently identified mutations and copy number changes in the 
      majority of genes with important clinical associations, such as TP53, TET2, 
      RUNX1, SRSF2, APC and ATM. Most importantly, NGS and CMA uncovered medically 
      actionable aberrations in 75.6% of cases normal by FISH/cytogenetics testing. NGS 
      identified mutations in 65.5% of samples normal by CMA, cytogenetics and FISH, 
      whereas CNVs were detected in 10.1% cases that were normal by all other 
      methodologies. Finally, FISH or cytogenetics, or both, were abnormal in 14.1% of 
      cases where NGS or CMA failed to detect any changes. Multiple mutations and CNVs 
      were found to coexist, with potential implications for patient stratification. 
      Thus, high throughput genomic tumor profiling through targeted DNA sequencing and 
      CNV analysis complements conventional methods and leads to more frequent 
      detection of actionable alterations.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Mukherjee, Sandeep
AU  - Mukherjee S
AD  - PathGroup, Nashville, TN.
FAU - Sathanoori, Malini
AU  - Sathanoori M
AD  - PathGroup, Nashville, TN.
FAU - Ma, Zeq
AU  - Ma Z
AD  - PathGroup, Nashville, TN.
FAU - Andreatta, Matthew
AU  - Andreatta M
AD  - PathGroup, Nashville, TN.
FAU - Lennon, Patrick A
AU  - Lennon PA
AD  - PathGroup, Nashville, TN. Electronic address: palennon@pathgroup.com.
FAU - Wheeler, Scott R
AU  - Wheeler SR
AD  - PathGroup, Nashville, TN.
FAU - Prescott, James L
AU  - Prescott JL
AD  - PathGroup, Nashville, TN.
FAU - Coldren, Christopher
AU  - Coldren C
AD  - PathGroup, Nashville, TN.
FAU - Casey, Terence
AU  - Casey T
AD  - PathGroup, Nashville, TN.
FAU - Rietz, Heather
AU  - Rietz H
AD  - PathGroup, Nashville, TN.
FAU - Fasig, Kristina
AU  - Fasig K
AD  - PathGroup, Nashville, TN.
FAU - Woodford, Randall
AU  - Woodford R
AD  - PathGroup, Nashville, TN.
FAU - Hartley, Taylor
AU  - Hartley T
AD  - PathGroup, Nashville, TN.
FAU - Spence, David
AU  - Spence D
AD  - PathGroup, Nashville, TN.
FAU - Donnelan, William
AU  - Donnelan W
AD  - Sarah Cannon Research Institute, Nashville, TN.
FAU - Berdeja, Jesus
AU  - Berdeja J
AD  - Sarah Cannon Research Institute, Nashville, TN.
FAU - Flinn, Ian
AU  - Flinn I
AD  - Sarah Cannon Research Institute, Nashville, TN.
FAU - Kozyr, Natalia
AU  - Kozyr N
AD  - Akesogen, Norcross, GA.
FAU - Bouzyk, Mark
AU  - Bouzyk M
AD  - Akesogen, Norcross, GA.
FAU - Correll, Mick
AU  - Correll M
AD  - GenoSpace, Cambridge, MA.
FAU - Ho, Hao
AU  - Ho H
AD  - PathGroup, Nashville, TN.
FAU - Kravtsov, Vladimir
AU  - Kravtsov V
AD  - PathGroup, Nashville, TN.
FAU - Tunnel, Dana
AU  - Tunnel D
AD  - PathGroup, Nashville, TN.
FAU - Chandra, Pranil
AU  - Chandra P
AD  - PathGroup, Nashville, TN.
LA  - eng
PT  - Journal Article
DEP - 20170814
PL  - United States
TA  - Cancer Genet
JT  - Cancer genetics
JID - 101539150
SB  - IM
MH  - Chromosomes, Human/*genetics
MH  - Cohort Studies
MH  - Cytogenetics/*methods
MH  - DNA Copy Number Variations/genetics
MH  - Genomics/*methods
MH  - High-Throughput Nucleotide Sequencing/*methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Mutation/genetics
MH  - Myeloproliferative Disorders/diagnosis/*genetics
MH  - Oligonucleotide Array Sequence Analysis/*methods
MH  - Tumor Burden
OTO - NOTNLM
OT  - Chromosomal microarray
OT  - actionable
OT  - genomic profiling
OT  - myeloid malignancy
OT  - next generation sequencing
EDAT- 2017/10/14 06:00
MHDA- 2017/10/31 06:00
CRDT- 2017/10/14 06:00
PHST- 2016/08/30 00:00 [received]
PHST- 2017/04/28 00:00 [revised]
PHST- 2017/07/27 00:00 [accepted]
PHST- 2017/10/14 06:00 [entrez]
PHST- 2017/10/14 06:00 [pubmed]
PHST- 2017/10/31 06:00 [medline]
AID - S2210-7762(17)30324-1 [pii]
AID - 10.1016/j.cancergen.2017.07.010 [doi]
PST - ppublish
SO  - Cancer Genet. 2017 Oct;216-217:128-141. doi: 10.1016/j.cancergen.2017.07.010. 
      Epub 2017 Aug 14.