PMID- 27341486
OWN - NLM
STAT- MEDLINE
DCOM- 20170525
LR  - 20180831
IS  - 1096-8652 (Electronic)
IS  - 0361-8609 (Linking)
VI  - 91
IP  - 10
DP  - 2016 Oct
TI  - FISHing in the dark: How the combination of FISH and conventional karyotyping 
      improves the diagnostic yield in CpG-stimulated chronic lymphocytic leukemia.
PG  - 978-83
LID - 10.1002/ajh.24452 [doi]
AB  - Despite significant advances in molecular genetic approaches, fluorescence in 
      situ hybridization (FISH) remains the gold standard for the diagnostic evaluation 
      of genomic aberrations in patients with chronic lymphocytic leukemia (CLL). 
      Efforts to improve the diagnostic utility of molecular cytogenetic testing have 
      led to the expansion of the traditional 4-probe CLL FISH panel. Not only do these 
      efforts increase the cost of testing, they remain hindered by the inherent 
      limitations of FISH studies - namely the inability to evaluate genomic changes 
      outside of the targeted loci. While array-based profiling and next generation 
      sequencing (NGS) have critically expanded our understanding of the molecular 
      pathogenesis of CLL, these methodologies are not routinely used by diagnostic 
      laboratories to evaluate copy number changes or the mutational profile of this 
      disease. Mitogenic stimulation of CLL specimens with CpG-oligonucleotide 
      (CpG-ODN) has been identified as a reliable and reproducible means of obtaining a 
      karyotype, facilitating a low-resolution genome-wide analysis. Across a cohort of 
      1255 CpG-ODN-stimulated CLL specimens, we describe the clinical utility 
      associated with the combinatorial use of FISH and karyotyping. Our testing 
      algorithm achieves a higher diagnostic yield ( approximately 10%) through the detection of 
      complex karyotypes, well-characterized chromosomal aberrations not covered by the 
      traditional CLL FISH panel and through the detection of concurrent secondary 
      malignancies. Moreover, the single cell nature of this approach permits the 
      evaluation of emerging new clinical concepts including clonal dynamics and clonal 
      evolution. This approach can be broadly applied by diagnostic laboratories to 
      improve the utility of traditional and molecular cytogenetic studies of CLL. Am. 
      J. Hematol. 91:978-983, 2016. (c) 2016 Wiley Periodicals, Inc.
CI  - (c) 2016 Wiley Periodicals, Inc.
FAU - Dubuc, Adrian M
AU  - Dubuc AM
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
AD  - Harvard Medical School, Boston, Massachusetts.
FAU - Davids, Matthew S
AU  - Davids MS
AD  - Harvard Medical School, Boston, Massachusetts.
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
FAU - Pulluqi, Mirela
AU  - Pulluqi M
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Pulluqi, Olja
AU  - Pulluqi O
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Hoang, Kevin
AU  - Hoang K
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
FAU - Hernandez-Sanchez, Jesus M
AU  - Hernandez-Sanchez JM
AD  - IBSAL, IBMCC, Centro de Investigacion del Cancer, Universidad de Salamanca-CSIC, 
      Salamanca, 37007, Spain.
FAU - Schlich, Cathy
AU  - Schlich C
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Hernandez-Rivas, Jesus M
AU  - Hernandez-Rivas JM
AD  - IBSAL, IBMCC, Centro de Investigacion del Cancer, Universidad de Salamanca-CSIC, 
      Salamanca, 37007, Spain.
AD  - Department of Hematology, Hospital Universitario de Salamanca, Salamanca, 37007, 
      Spain.
FAU - Brown, Jennifer R
AU  - Brown JR
AD  - Harvard Medical School, Boston, Massachusetts.
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
FAU - Dal Cin, Paola
AU  - Dal Cin P
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. 
      pdalcin@partners.org.
AD  - Harvard Medical School, Boston, Massachusetts. pdalcin@partners.org.
LA  - eng
PT  - Journal Article
DEP - 20160722
PL  - United States
TA  - Am J Hematol
JT  - American journal of hematology
JID - 7610369
RN  - 0 (CPG-oligonucleotide)
RN  - 0 (Mitogens)
RN  - 0 (Oligodeoxyribonucleotides)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Chromosome Aberrations
MH  - Clone Cells/pathology
MH  - Cytogenetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Karyotyping/*methods
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*diagnosis/etiology/genetics
MH  - Middle Aged
MH  - Mitogens/pharmacology
MH  - Neoplasms, Second Primary/diagnosis
MH  - Oligodeoxyribonucleotides/pharmacology
MH  - Single-Cell Analysis
MH  - Young Adult
EDAT- 2016/06/25 06:00
MHDA- 2017/05/26 06:00
CRDT- 2016/06/25 06:00
PHST- 2015/12/04 00:00 [received]
PHST- 2016/05/26 00:00 [revised]
PHST- 2016/06/17 00:00 [accepted]
PHST- 2016/06/25 06:00 [entrez]
PHST- 2016/06/25 06:00 [pubmed]
PHST- 2017/05/26 06:00 [medline]
AID - 10.1002/ajh.24452 [doi]
PST - ppublish
SO  - Am J Hematol. 2016 Oct;91(10):978-83. doi: 10.1002/ajh.24452. Epub 2016 Jul 22.