PRPS1) [164, 170–172], which can validate the subsequent drug
resistance analyses in cellular level.
NGS-based GWASs become more and more popular as well
because all variants (both common and rare) can be detected with-
out array-based imputation, which may induce genotyping error or
no call for non-probed variants. Importantly, causal variants can be
detected directly without fine-mapping procedure or even missing
for post-GWAS effects [102]. Also, burden test can be conducted
by combining all potential functional rare variants within one gene
and used for gene-based correlation [173]. In research of ALL, rare
variants inETV6[174] andCDKN2A[92] were identified by
target sequencing and illustrated significant association with ALL
susceptibility. On the other hand, causal mutations for rare familial
ALL cases were also identified by exome sequencing, which is very
difficult to achieve due to the limited numbers of patients for family
pedigree (e.g., most of the childhood ALL patients died before they
have their own children before the 1960s). For instance, germline
mutations ofPAX5 were found in all ALL patients from two
unrelated kindreds [175], and a nonsense mutation inETV6was
found in an ALL patient and her three children, two of which also
catch ALL [174]. With the development of the whole genome
sequencing, more causal variants were expected to be identified
before onset of diseases for prevention, etc.
Collectively, more and more NGS-based studies have been
conducted in ALL research, not only broadening our insight to
understand the complicated mechanisms of such diseases in terms
of leukemogenesis and drug response but also providing the oppor-
tunities for us to divide the patients into plenty of different molec-
ular subtypes and design the best individualized regimen. Besides,
the NGS technologies are still under rapid development; more and
more basic research findings are expected to be translated into the
clinical practice.5 Summary
In this section, we used ALL as a disease model to illustrate the
translational researches with the development of technology and
strategy used in genetic studies. Plenty of ALL-related alteration
has been found in eras of genomic researches (Fig.4). Thanks to
the combination of these basic research effects and the develop-
ment new drugs/treatment strategies, treatment outcomes of ALL
have greatly improved and are still in progress, successful experi-
ences of which are also valuable for treatments of other tumors.Insights of Acute Lymphoblastic Leukemia with Development of Genomic... 405