PMID- 35064090
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20220722
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 119
IP  - 4
DP  - 2022 Jan 25
TI  - A large fraction of trisomy 12, 17p(-), and 11q(-) CLL cases carry unidentified 
      microdeletions of miR-15a/16-1.
LID - 10.1073/pnas.2118752119 [doi]
LID - e2118752119
AB  - Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is 
      characterized by chromosomal aberrations including 13q, 11q, and 17p deletions 
      and a trisomy of chromosome 12 (T12). 13q deletions are often associated with 11q 
      and 17p deletions in aggressive cases. Conversely, T12 CLLs show a variable 
      prognosis, and association with 13q deletions is uncommon. The miR-15a/16-1 
      cluster is the functional target of 13q deletions, leading to BCL2 
      overexpression. Chromosomal aberrations in CLL are associated with prognosis, and 
      their identification is carried out by fluorescence in situ hybridization (FISH). 
      Since standard FISH only detects large deletions, we investigated the presence of 
      undetected microdeletions targeting miR-15a/16-1 in CLL cases. We found that  approximately 34% 
      of CLL samples show an unreported loss of the miR-15a/16-1 locus regardless of 
      their cytogenetic profile. Interestingly, 15 out of 39 ( approximately 39%) of all CLLs with 
      T12, carry microdeletions of miR-15a/16-1, indicating that, in patients with T12, 
      miR-15a/16-1 are mostly inactivated by microdeletions. In addition,  approximately 40% of CLL 
      cases bearing T12, 17p(-), and 11q(-) showed unidentified microdeletions of 
      miR-15a/16-1, suggesting that miR-15a/16-1 loss cooperates with such chromosomal 
      alterations in CLL. These data may have clinical relevance for the successful 
      stratification of patients for treatment.
CI  - Copyright (c) 2022 the Author(s). Published by PNAS.
FAU - Pepe, Felice
AU  - Pepe F
AD  - Department of Cancer Biology and Genetics, The Ohio State University, Columbus, 
      OH 43210.
AD  - Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
FAU - Rassenti, Laura Z
AU  - Rassenti LZ
AD  - Department of Medicine, University of California San Diego, La Jolla, CA 92093.
FAU - Pekarsky, Yuri
AU  - Pekarsky Y
AD  - Department of Cancer Biology and Genetics, The Ohio State University, Columbus, 
      OH 43210.
AD  - Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
FAU - Labanowska, Jadwiga
AU  - Labanowska J
AD  - Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
AD  - Department of Pathology, The Ohio State University, Columbus, OH 43210.
FAU - Nakamura, Tatsuya
AU  - Nakamura T
AUID- ORCID: 0000-0002-9011-6001
AD  - Department of Cancer Biology and Genetics, The Ohio State University, Columbus, 
      OH 43210.
AD  - Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
FAU - Nigita, Giovanni
AU  - Nigita G
AD  - Department of Cancer Biology and Genetics, The Ohio State University, Columbus, 
      OH 43210.
AD  - Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
FAU - Kipps, Thomas J
AU  - Kipps TJ
AD  - Department of Medicine, University of California San Diego, La Jolla, CA 92093.
FAU - Balatti, Veronica
AU  - Balatti V
AD  - Department of Cancer Biology and Genetics, The Ohio State University, Columbus, 
      OH 43210; veronica.balatti@osumc.edu carlo.croce@osumc.edu.
AD  - Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
FAU - Croce, Carlo M
AU  - Croce CM
AUID- ORCID: 0000-0003-3788-1457
AD  - Department of Cancer Biology and Genetics, The Ohio State University, Columbus, 
      OH 43210; veronica.balatti@osumc.edu carlo.croce@osumc.edu.
AD  - Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
LA  - eng
GR  - R35 CA197706/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (MIRN15 microRNA, human)
RN  - 0 (MIRN16 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - *Chromosome Deletion
MH  - *Chromosomes, Human, Pair 11
MH  - *Chromosomes, Human, Pair 12
MH  - *Chromosomes, Human, Pair 17
MH  - DNA Copy Number Variations
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis/*genetics
MH  - MicroRNAs/*genetics
MH  - *Trisomy
PMC - PMC8794880
OTO - NOTNLM
OT  - 13q deletion
OT  - CLL
OT  - miR-15a/16-1
OT  - trisomy 12
COIS- The authors declare no competing interest.
EDAT- 2022/01/23 06:00
MHDA- 2022/03/01 06:00
PMCR- 2022/07/21
CRDT- 2022/01/22 05:43
PHST- 2021/12/21 00:00 [accepted]
PHST- 2022/01/22 05:43 [entrez]
PHST- 2022/01/23 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
PHST- 2022/07/21 00:00 [pmc-release]
AID - 2118752119 [pii]
AID - 202118752 [pii]
AID - 10.1073/pnas.2118752119 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2118752119. doi: 
      10.1073/pnas.2118752119.