PMID- 30830578
OWN - NLM
STAT- MEDLINE
DCOM- 20190502
LR  - 20200225
IS  - 1865-3774 (Electronic)
IS  - 0925-5710 (Linking)
VI  - 109
IP  - 5
DP  - 2019 May
TI  - A novel method of amplified fluorescent in situ hybridization for detection of 
      chromosomal microdeletions in B cell lymphoma.
PG  - 593-602
LID - 10.1007/s12185-019-02617-x [doi]
AB  - Chromosomal microdeletions frequently cause loss of prognostically relevant tumor 
      suppressor genes in hematologic malignancies; however, detection of minute 
      deletions by conventional methods for chromosomal analysis, such as G-banding and 
      fluorescence in situ hybridization (FISH), is difficult due to their low 
      resolution. Here, we describe a new diagnostic modality that enables detection of 
      chromosomal microdeletions, using CDKN2A gene deletion in B cell lymphomas (BCLs) 
      as an example. In this method, which we refer to as amplified-FISH (AM-FISH), a 
      31-kb fluorescein isothiocyanate (FITC)-conjugated DNA probe encoding only CDKN2A 
      was first hybridized with the chromosome, and then labeled with Alexa Fluor 
      488-conjugated anti-FITC secondary antibody to increase sensitivity. CDKN2A 
      signals were equally identifiable by AM-FISH and conventional FISH in normal 
      mononuclear blood cells. In contrast, when two BCL cell lines lacking CDKN2A were 
      analyzed, CDKN2A signals were not detected by AM-FISH, whereas conventional FISH 
      yielded false signals. Furthermore, AM-FISH detected CDKN2A deletions in two BCL 
      patients with 9p21 microdeletions, which were not detected by conventional FISH. 
      These results suggest that AM-FISH is a highly sensitive, specific, and simple 
      method for diagnosis of chromosomal microdeletions.
FAU - Mizuno, Yoshimi
AU  - Mizuno Y
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Chinen, Yoshiaki
AU  - Chinen Y
AUID- ORCID: 0000-0001-8966-2876
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan. 
      y-chinen@koto.kpu-m.ac.jp.
FAU - Tsukamoto, Taku
AU  - Tsukamoto T
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Takimoto-Shimomura, Tomoko
AU  - Takimoto-Shimomura T
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Matsumura-Kimoto, Yayoi
AU  - Matsumura-Kimoto Y
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Fujibayashi, Yuto
AU  - Fujibayashi Y
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Kuwahara-Ota, Saeko
AU  - Kuwahara-Ota S
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Fujino, Takahiro
AU  - Fujino T
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Nishiyama, Daichi
AU  - Nishiyama D
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Shimura, Yuji
AU  - Shimura Y
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Kobayashi, Tsutomu
AU  - Kobayashi T
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Horiike, Shigeo
AU  - Horiike S
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Taniwaki, Masafumi
AU  - Taniwaki M
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
FAU - Kuroda, Junya
AU  - Kuroda J
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
LA  - eng
GR  - JP16K21284/Japan Society for the Promotion of Science/
GR  - 16K09856/Ministry of Education, Culture, Sports, Science and Technology/
GR  - 17ck0106348h0001/Japan Agency for Medical Research and Development/
PT  - Journal Article
DEP - 20190304
PL  - Japan
TA  - Int J Hematol
JT  - International journal of hematology
JID - 9111627
RN  - 0 (CDKN2A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
SB  - IM
MH  - Cell Line, Tumor
MH  - *Chromosome Deletion
MH  - Chromosomes, Human/*genetics/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Lymphoma, B-Cell/*genetics/*metabolism/pathology
OTO - NOTNLM
OT  - Amplified-FISH
OT  - CDKN2A
OT  - Fluorescence in situ hybridization (FISH)
OT  - Hematologic malignancy
OT  - Microdeletion
EDAT- 2019/03/05 06:00
MHDA- 2019/05/03 06:00
CRDT- 2019/03/05 06:00
PHST- 2018/11/26 00:00 [received]
PHST- 2019/02/12 00:00 [accepted]
PHST- 2019/02/09 00:00 [revised]
PHST- 2019/03/05 06:00 [pubmed]
PHST- 2019/05/03 06:00 [medline]
PHST- 2019/03/05 06:00 [entrez]
AID - 10.1007/s12185-019-02617-x [pii]
AID - 10.1007/s12185-019-02617-x [doi]
PST - ppublish
SO  - Int J Hematol. 2019 May;109(5):593-602. doi: 10.1007/s12185-019-02617-x. Epub 
      2019 Mar 4.