PMID- 32949441
OWN - NLM
STAT- MEDLINE
DCOM- 20220104
LR  - 20220104
IS  - 1521-2254 (Electronic)
IS  - 1099-498X (Linking)
VI  - 23
IP  - 1
DP  - 2021 Jan
TI  - Breakpoint mapping of a t(9;22;12) chronic myeloid leukaemia patient with e14a3 
      BCR-ABL1 transcript using Nanopore sequencing.
PG  - e3276
LID - 10.1002/jgm.3276 [doi]
AB  - BACKGROUND: The genetic changes in chronic myeloid leukaemia (CML) have been well 
      established, although challenges persist in cases with rare fusion transcripts or 
      complex variant translocations. Here, we present a CML patient with e14a3 
      BCR-ABL1 transcript and t(9;22;12) variant Philadelphia (Ph) chromosome. METHODS: 
      Cytogenetic analysis and fluorescence in situ hybridization (FISH) was performed 
      to identify the chromosomal aberrations and gene fusions. Rare fusion transcript 
      was verified by a reverse transcription-polymerase chain reaction (RT-PCR). 
      Breakpoints were characterized and validated using Oxford Nanopore Technologies 
      (ONT) (Oxford, UK) and Sanger sequencing, respectively. RESULTS: The karyotype 
      showed the translocation t(9;22;12)(q34;q11.2;q24) [20] and FISH indicated 40% 
      positive BCR-ABL1 fusion signals. The RT-PCR suggested e14a3 type fusion 
      transcript. The ONT sequencing analysis identified specific positions of 
      translocation breakpoints: chr22:23633040-chr9:133729579, 
      chr12:121567595-chr22:24701405, which were confirmed using Sanger sequencing. The 
      patient achieved molecular remission 3 months after imatinib therapy. 
      CONCLUSIONS: The present study indicates Nanopore sequencing as a valid strategy, 
      which can characterize breakpoints precisely in special clinical cases with 
      atypical structural variations. CML patients with e14a3 transcripts may have good 
      clinical course in the tyrosine kinase inhibitor era, as reviewed here.
CI  - (c) 2020 John Wiley & Sons, Ltd.
FAU - Zhao, Hu
AU  - Zhao H
AD  - Department of Haematology, The Affiliated Zhuzhou Hospital, XiangYa Medical 
      College, Central South University, Zhuzhou, Hunan, China.
FAU - Chen, Yuan
AU  - Chen Y
AD  - Department of Haematology, The Affiliated Zhuzhou Hospital, XiangYa Medical 
      College, Central South University, Zhuzhou, Hunan, China.
FAU - Shen, Chanjuan
AU  - Shen C
AD  - Department of Haematology, The Affiliated Zhuzhou Hospital, XiangYa Medical 
      College, Central South University, Zhuzhou, Hunan, China.
FAU - Li, Lingshu
AU  - Li L
AD  - Department of Haematology, The Affiliated Zhuzhou Hospital, XiangYa Medical 
      College, Central South University, Zhuzhou, Hunan, China.
FAU - Li, Qingzhao
AU  - Li Q
AD  - Department of Haematology, The Affiliated Zhuzhou Hospital, XiangYa Medical 
      College, Central South University, Zhuzhou, Hunan, China.
FAU - Tan, Kui
AU  - Tan K
AD  - Department of Haematology, The Affiliated Zhuzhou Hospital, XiangYa Medical 
      College, Central South University, Zhuzhou, Hunan, China.
FAU - Huang, Huang
AU  - Huang H
AD  - Department of Haematology, The Affiliated Zhuzhou Hospital, XiangYa Medical 
      College, Central South University, Zhuzhou, Hunan, China.
FAU - Hu, Guoyu
AU  - Hu G
AUID- ORCID: 0000-0003-0293-5080
AD  - Department of Haematology, The Affiliated Zhuzhou Hospital, XiangYa Medical 
      College, Central South University, Zhuzhou, Hunan, China.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201001
PL  - England
TA  - J Gene Med
JT  - The journal of gene medicine
JID - 9815764
RN  - 0 (BCR-ABL1 fusion protein, human)
RN  - 0 (Biomarkers)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Base Sequence
MH  - Biomarkers
MH  - Bone Marrow Cells
MH  - *Chromosome Breakpoints
MH  - Cytogenetic Analysis
MH  - Fusion Proteins, bcr-abl/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Nanopore Sequencing
MH  - *Philadelphia Chromosome
MH  - Sequence Analysis, DNA
MH  - Transcription, Genetic
OTO - NOTNLM
OT  - cancer-leukemia/hematologic
OT  - haematology
OT  - molecular genetics
EDAT- 2020/09/20 06:00
MHDA- 2022/01/05 06:00
CRDT- 2020/09/19 12:06
PHST- 2020/07/15 00:00 [received]
PHST- 2020/09/03 00:00 [revised]
PHST- 2020/09/14 00:00 [accepted]
PHST- 2020/09/20 06:00 [pubmed]
PHST- 2022/01/05 06:00 [medline]
PHST- 2020/09/19 12:06 [entrez]
AID - 10.1002/jgm.3276 [doi]
PST - ppublish
SO  - J Gene Med. 2021 Jan;23(1):e3276. doi: 10.1002/jgm.3276. Epub 2020 Oct 1.