PMID- 26702937
OWN - NLM
STAT- MEDLINE
DCOM- 20160623
LR  - 20181113
IS  - 2210-7762 (Print)
VI  - 209
IP  - 1-2
DP  - 2016 Jan-Feb
TI  - Clonal evolution and clinical significance of copy number neutral loss of 
      heterozygosity of chromosome arm 6p in acquired aplastic anemia.
PG  - 1-10
LID - S2210-7762(15)00211-2 [pii]
LID - 10.1016/j.cancergen.2015.10.002 [doi]
AB  - Acquired aplastic anemia (aAA) results from the T cell-mediated autoimmune 
      destruction of hematopoietic stem cells. Factors predicting response to immune 
      suppression therapy (IST) or development of myelodysplastic syndrome (MDS) are 
      beginning to be elucidated. Our recent data suggest most patients with aAA 
      treated with IST develop clonal somatic genetic alterations in hematopoietic 
      cells. One frequent acquired abnormality is copy-number neutral loss of 
      heterozygosity on chromosome 6p (6p CN-LOH) involving the human leukocyte antigen 
      (HLA) locus. We hypothesized that because 6p CN-LOH clones may arise from 
      selective pressure to escape immune surveillance through deletion of HLA alleles, 
      the development of 6p CN-LOH may affect response to IST. We used single 
      nucleotide polymorphism array genotyping and targeted next-generation sequencing 
      of HLA alleles to assess frequency of 6p CN-LOH, identity of HLA alleles lost 
      through 6p CN-LOH, and impact of 6p CN-LOH on response to IST. 6p CN-LOH clones 
      were present in 11.3% of patients, remained stable over time, and were not 
      associated with development of MDS-defining cytogenetic abnormalities. Notably, 
      no patient with 6p CN-LOH treated with IST achieved a complete response. In 
      summary, clonal 6p CN-LOH in aAA defines a unique subgroup of patients that may 
      provide insights into hematopoietic clonal evolution.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Betensky, Marisol
AU  - Betensky M
AD  - Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of 
      Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
FAU - Babushok, Daria
AU  - Babushok D
AD  - Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of 
      Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
FAU - Roth, Jacquelyn J
AU  - Roth JJ
AD  - Division of Human Genetics, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphia, PA, USA.
FAU - Mason, Philip J
AU  - Mason PJ
AD  - Department of Pediatrics, Perelman School of Medicine at the University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Biegel, Jaclyn A
AU  - Biegel JA
AD  - Division of Human Genetics, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphia, PA, USA.
FAU - Busse, Tracy M
AU  - Busse TM
AD  - Division of Human Genetics, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphia, PA, USA.
FAU - Li, Yimei
AU  - Li Y
AD  - Department of Biostatistics and Epidemiology, Perelman School of Medicine at the 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Lind, Curt
AU  - Lind C
AD  - Department of Pathology and Laboratory Medicine, Division of Genomic Diagnostics, 
      Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of 
      Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
FAU - Papazoglou, Anna
AU  - Papazoglou A
AD  - Department of Pathology and Laboratory Medicine, Division of Genomic Diagnostics, 
      Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of 
      Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
FAU - Monos, Dimitri
AU  - Monos D
AD  - Department of Pathology and Laboratory Medicine, Division of Genomic Diagnostics, 
      Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of 
      Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
FAU - Podsakoff, Gregory
AU  - Podsakoff G
AD  - Office of Clinical and Translational Research, Children's Hospital of 
      Philadelphia, Philadelphia, PA, USA.
FAU - Bessler, Monica
AU  - Bessler M
AD  - Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of 
      Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
FAU - Olson, Timothy S
AU  - Olson TS
AD  - Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of 
      Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division 
      of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA. Electronic address: olsont@email.chop.edu.
LA  - eng
GR  - NHLBI/NIH K12 HL097064/PHS HHS/United States
GR  - T32 GM008638/GM/NIGMS NIH HHS/United States
GR  - T32 HL007150/HL/NHLBI NIH HHS/United States
GR  - R01 HL097064/HL/NHLBI NIH HHS/United States
GR  - UL1 TR000003/TR/NCATS NIH HHS/United States
GR  - K12 HL087064/HL/NHLBI NIH HHS/United States
GR  - UL1TR000003/TR/NCATS NIH HHS/United States
GR  - NIH/NCI 5R01-CA105312-1/CA/NCI NIH HHS/United States
GR  - K08 HL122306/HL/NHLBI NIH HHS/United States
GR  - P30 CA016520/CA/NCI NIH HHS/United States
GR  - K12 HL087064/HL/NHLBI NIH HHS/United States
GR  - R01 CA105312/CA/NCI NIH HHS/United States
GR  - NIGMS T32-GM008638/PHS HHS/United States
GR  - R24 DK103001/DK/NIDDK NIH HHS/United States
GR  - NIH/NIDDK R24DK103001/PHS HHS/United States
GR  - NHLBI 5T32HL007150-38/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20151030
PL  - United States
TA  - Cancer Genet
JT  - Cancer genetics
JID - 101539150
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anemia, Aplastic/*genetics
MH  - Child
MH  - Child, Preschool
MH  - *Chromosomes, Human, Pair 6
MH  - *Clonal Evolution
MH  - *DNA Copy Number Variations
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - *Loss of Heterozygosity
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Young Adult
PMC - PMC4738084
MID - NIHMS734665
OTO - NOTNLM
OT  - Aplastic anemia
OT  - clonal evolution
OT  - single nucleotide polymorphism array
EDAT- 2015/12/26 06:00
MHDA- 2016/06/24 06:00
PMCR- 2017/01/01
CRDT- 2015/12/26 06:00
PHST- 2015/10/16 00:00 [received]
PHST- 2015/10/19 00:00 [accepted]
PHST- 2015/12/26 06:00 [entrez]
PHST- 2015/12/26 06:00 [pubmed]
PHST- 2016/06/24 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - S2210-7762(15)00211-2 [pii]
AID - 10.1016/j.cancergen.2015.10.002 [doi]
PST - ppublish
SO  - Cancer Genet. 2016 Jan-Feb;209(1-2):1-10. doi: 10.1016/j.cancergen.2015.10.002. 
      Epub 2015 Oct 30.