Open AccessHighly precise breakpoint detection of chromosome balanced translocation in chronic myelogenous leukaemia: Case series
Author(s) -
Yang Chuanchun,
Cui Xiaoli,
Xu Lei,
Zhang Qian,
Tang Shanmei,
Zhang Mengmeng,
Xie Ni
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17500
Subject(s) - breakpoint , chromosomal translocation , breakpoint cluster region , sanger sequencing , biology , chronic myelogenous leukemia , chromosome , genetics , karyotype , abl , philadelphia chromosome , dna sequencing , gene , leukemia , tyrosine kinase , signal transduction
Chronic myelogenous leukaemia (CML) has a special phenomenon of chromosome translocation, which is called Philadelphia chromosome translocation. However, the detailed connection of this structure is troublesome and expensive to be identified. Low‐coverage whole genome sequencing (LCWGS) could not only detect the previously unknown chromosomal translocation, but also provide the breakpoint candidate small region (with an accuracy of ±200 bases). Importantly, the sequencing cost of LCWGS is about US$300. Then, with the Sanger DNA sequencing, the precise breakpoint can be determined at a single base level. In our project, with LCWGS, BCR and ABL1 are successfully identified to be disrupted in three CML patients (at chr22:23,632,356 and chr9:133,590,450; chr22:23,633,748 and chr9:133,635,781; chr22: 23,631,831 and chr9:133,598,513, respectively). Due to the reconnection after chromosome breakage, classical fusion gene (BCR::ABL1) was found in bone marrow and peripheral blood. The precise breakpoints were helpful to investigate the pathogenic mechanism of CML and could better guide the classification of CML subtypes. This LCWGS method is universal and can be used to detect all diseases related to chromosome variation, such as solid tumours, liquid tumours and birth defects.