PMID- 7544647
OWN - NLM
STAT- MEDLINE
DCOM- 19951003
LR  - 20220408
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 86
IP  - 5
DP  - 1995 Sep 1
TI  - Refined mapping of genomic rearrangements involving the short arm of chromosome 9 
      in acute lymphoblastic leukemias and other hematologic malignancies.
PG  - 1931-8
AB  - Deletions of chromosomal band 9p21 have been detected in various tumor types as 
      well as in more than 20% of acute lymphoblastic leukemia (ALL). These deletions 
      frequently include the entire interferon (IFN) gene cluster as well as the 
      methylthioadenosine phosphorylase (MTAP) gene. Recently, the CDKN2 gene 
      (p16INK4A, MTS I, CDK41) was proposed as a candidate tumor-suppressor gene on 
      9p21 because it is frequently deleted in cell lines derived from multiple tumor 
      types. To determine if CDKN2 or another closely related gene on 9p is the target 
      of 9p deletions in ALL and other hematologic malignancies, we analyzed 20 primary 
      patient samples (13 ALL, 2 acute myeloid leukemias [AML], and 5 non-Hodgkin's 
      lymphomas [NHL]) with 9p rearrangements using Southern blot analysis, 
      fluorescence in situ hybridization (FISH), and single-strand conformation 
      polymorphism (SSCP) for alterations of CDKN2. Homozygous deletions of the 
      CDKN2/CDKN2B (p15) region were detected in 10 cases (50%; 6 ALL, 2 AML, and 2 
      NHL). In 1 additional case, the intensity of the Southern blot band was 
      significantly reduced, suggesting a CDKN2 deletion in a subpopulation of the 
      malignant cells. No CDKN2 or CDKN2B rearrangements were seen. The IFN gene 
      cluster was homozygously deleted in 2 of 15 (13%) analyzed cases, whereas the 
      MTAP gene was deleted in 6 of 15 cases (40%). In addition, hemizygous deletions 
      of the CDKN2 region were identified in 6 ALL cases using interphase FISH. No 
      point mutation of the coding region of CDKN2 was detected by SSCP in these cases. 
      We conclude that CDKN2 is the most frequently homozygously deleted marker on 9p. 
      The absence of point mutations in the coding region of CDKN2 in cases with 
      hemizygous 9p deletions and the frequent codeletion of MTAP, CDKN2B, and other 
      yet unidentified neighboring genes suggest that the simultaneous deletion of 
      these genes may be necessary for the selective growth advantage of malignant 
      cells.
FAU - Dreyling, M H
AU  - Dreyling MH
AD  - Department of Medicine, University of Chicago, IL 60637, USA.
FAU - Bohlander, S K
AU  - Bohlander SK
FAU - Le Beau, M M
AU  - Le Beau MM
FAU - Olopade, O I
AU  - Olopade OI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Carrier Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 9008-11-1 (Interferons)
RN  - EC 2.4.2.1 (Purine-Nucleoside Phosphorylase)
RN  - EC 2.4.2.28 (5'-methylthioadenosine phosphorylase)
SB  - IM
GS  - CDK4I
GS  - CDKN2
GS  - IFN
GS  - MTAP
GS  - MTS1
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Blotting, Southern
MH  - Bone Marrow/pathology
MH  - Bone Marrow Cells
MH  - Carrier Proteins/blood/*genetics
MH  - Cells, Cultured
MH  - Child, Preschool
MH  - *Chromosome Aberrations
MH  - *Chromosome Deletion
MH  - *Chromosome Disorders
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 9
MH  - Cyclin-Dependent Kinase Inhibitor p16
MH  - Female
MH  - Gene Deletion
MH  - Gene Rearrangement
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interferons/genetics
MH  - Karyotyping
MH  - Leukemia, Myeloid, Acute/blood/*genetics/pathology
MH  - Lymphoma, Non-Hodgkin/blood/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Monocytes/pathology
MH  - Multigene Family
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood/*genetics/pathology
MH  - Purine-Nucleoside Phosphorylase/genetics
EDAT- 1995/09/01 00:00
MHDA- 1995/09/01 00:01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 1995/09/01 00:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
AID - S0006-4971(20)76353-6 [pii]
PST - ppublish
SO  - Blood. 1995 Sep 1;86(5):1931-8.