PMID- 31425927
OWN - NLM
STAT- MEDLINE
DCOM- 20200505
LR  - 20201207
IS  - 2210-7762 (Print)
VI  - 238
DP  - 2019 Oct
TI  - Masked hypodiploidy: Hypodiploid acute lymphoblastic leukemia (ALL) mimicking 
      hyperdiploid ALL in children: A report from the Children's Oncology Group.
PG  - 62-68
LID - S2210-7762(19)30118-8 [pii]
LID - 10.1016/j.cancergen.2019.07.009 [doi]
AB  - Hyperdiploidy with greater than 50 chromosomes is usually associated with 
      favorable prognosis in pediatric acute lymphoblastic leukemia (ALL), whereas 
      hypodiploidy with </=43 chromosomes is associated with extremely poor prognosis. 
      Sometimes, hypodiploidy is "masked" and patients do not have a karyotypically 
      visible clone with </=43 chromosomes. Instead, their abnormal karyotypes contain 
      50-78 or more chromosomes from doubling of previously hypodiploid cells. When the 
      hypodiploid and doubled hyperdiploid clones are both present, patients can be 
      identified by traditional test methods [karyotype, DNA Index (DI), fluorescence 
      in situ hybridization (FISH)], but the incidence of masked hypodiploid cases in 
      which only the doubled clone is visible is unknown. We analyzed 7013 patients 
      with B-ALL enrolled in COG AALL03B1 (2003-2011) for whom chromosome studies were 
      available. Of 115 patients with hypodiploidy (25-39 chromosomes), karyotypes of 
      40 showed only the hypodiploid clone, 47 showed mosaicism with both hypodiploid 
      and hyperdiploid (doubled) karyotypes, and 28 with masked hypodiploidy showed 
      only a hyperdiploid (doubled) clone. Unique karyotypic signatures were 
      identified, and widespread loss of heterozygosity (LOH) was seen in the 
      microsatellite panel for all patients with masked hypodiploidy. An increased 
      awareness of the unusual karyotypic profile associated with a doubled hypodiploid 
      clone and coordinated use of DI, FISH, and LOH studies when indicated can 
      identify patients with masked hypodiploidy and allow appropriate treatment 
      selection.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Carroll, Andrew J
AU  - Carroll AJ
AD  - Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA. 
      Electronic address: acarroll@uab.edu.
FAU - Shago, Mary
AU  - Shago M
AD  - Department of Pathobiology and Laboratory Medicine, University of Toronto, 
      Toronto, ON, Canada.
FAU - Mikhail, Fady M
AU  - Mikhail FM
AD  - Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
FAU - Raimondi, Susana C
AU  - Raimondi SC
AD  - Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
FAU - Hirsch, Betsy A
AU  - Hirsch BA
AD  - Department of Laboratory Medicine and Pathology, University of Minnesota Medical 
      School, Minneapolis, MN, USA.
FAU - Loh, Mignon L
AU  - Loh ML
AD  - Department of Pediatrics, UCSF Medical Center-Mission Bay, San Francisco, CA, 
      USA.
FAU - Raetz, Elizabeth A
AU  - Raetz EA
AD  - Department of Pediatrics, New York University Medical Center, New York, NY, USA.
FAU - Borowitz, Michael J
AU  - Borowitz MJ
AD  - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
FAU - Wood, Brent L
AU  - Wood BL
AD  - Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
FAU - Maloney, Kelly W
AU  - Maloney KW
AD  - Children's Hospital of Colorado, Aurora, CO, USA.
FAU - Mattano, Leonard A Jr
AU  - Mattano LA Jr
AD  - HARP Pharma Consulting, Mystic, CT, USA.
FAU - Larsen, Eric C
AU  - Larsen EC
AD  - Maine Children's Cancer Program, Scarborough, ME, USA.
FAU - Gastier-Foster, Julie
AU  - Gastier-Foster J
AD  - Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, 
      USA; Department of Pathology, The Ohio State University, Columbus, OH, USA.
FAU - Stonerock, Eileen
AU  - Stonerock E
AD  - Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, 
      USA.
FAU - Ell, Denise
AU  - Ell D
AD  - Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, 
      USA.
FAU - Kahwash, Samir
AU  - Kahwash S
AD  - Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, 
      USA.
FAU - Devidas, Meenakshi
AU  - Devidas M
AD  - Department of Biostatistics, University of Florida, Gainesville, FL, USA.
FAU - Harvey, Richard C
AU  - Harvey RC
AD  - University of New Mexico Cancer Center, Albuquerque, NM, USA.
FAU - Chen, I-Ming L
AU  - Chen IL
AD  - University of New Mexico Cancer Center, Albuquerque, NM, USA.
FAU - Willman, Cheryl L
AU  - Willman CL
AD  - University of New Mexico Cancer Center, Albuquerque, NM, USA.
FAU - Hunger, Stephen P
AU  - Hunger SP
AD  - Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Winick, Naomi J
AU  - Winick NJ
AD  - Department of Pediatrics, University of Texas Southwestern Medical Center, 
      Dallas, TX, USA.
FAU - Carroll, William L
AU  - Carroll WL
AD  - Department of Pediatrics, New York University Medical Center, New York, NY, USA.
FAU - Rao, Kathleen W
AU  - Rao KW
AD  - Department of Pathology and Laboratory Medicine, University of North Carolina 
      School of Medicine, Chapel Hill, NC, USA.
FAU - Heerema, Nyla A
AU  - Heerema NA
AD  - Department of Pathology, The Ohio State University, Columbus, OH, USA.
LA  - eng
GR  - U10 CA098543/CA/NCI NIH HHS/United States
GR  - U10 CA180886/CA/NCI NIH HHS/United States
GR  - U10 CA180899/CA/NCI NIH HHS/United States
GR  - UG1 CA233324/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190730
PL  - United States
TA  - Cancer Genet
JT  - Cancer genetics
JID - 101539150
SB  - IM
MH  - Child
MH  - Chromosomes, Human
MH  - *Diploidy
MH  - Humans
MH  - Karyotyping
MH  - Mosaicism
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics
PMC - PMC6768693
MID - NIHMS1536000
OTO - NOTNLM
OT  - B-ALL
OT  - Cytogenetics
OT  - Doubling
OT  - Hypodiploid
OT  - Low-hypodiploid
OT  - Near-haploid
COIS- Conflict of Interest: The authors declare no conflict of interest. All authors 
      read and approved the first version of the manuscript.
EDAT- 2019/08/20 06:00
MHDA- 2020/05/06 06:00
PMCR- 2020/10/01
CRDT- 2019/08/20 06:00
PHST- 2019/03/26 00:00 [received]
PHST- 2019/06/28 00:00 [revised]
PHST- 2019/07/27 00:00 [accepted]
PHST- 2019/08/20 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2019/08/20 06:00 [entrez]
PHST- 2020/10/01 00:00 [pmc-release]
AID - S2210-7762(19)30118-8 [pii]
AID - 10.1016/j.cancergen.2019.07.009 [doi]
PST - ppublish
SO  - Cancer Genet. 2019 Oct;238:62-68. doi: 10.1016/j.cancergen.2019.07.009. Epub 2019 
      Jul 30.