Oxford-Nanopore eBook - 16

Using Nanopore
Sequencing to
Study Full-Length
Transcripts and
Splicing Isoforms

Alison Tang (UC Santa
Cruz) describes her lab's
studies on full-length
transcript characterization
of the mutated SF3B1
transcriptome in chronic
lymphocytic leukemia
hronic Lymphocytic Leukemia
(CLL) is the most common form of
blood cancer in adults, with an esti-

mated incidence of up to 5.5 per 100,000
people worldwide. Alison Tang, a graduate
student in the lab of Angela Brooks at the
University of California, Santa Cruz, has
been studying one of the most frequently
mutated genes in CLL (and other cancers)-
the gene SF3B1, which encodes a splicing
factor. Mutations in SF3B1 are associated
with poor patient prognosis, but how they
actually contribute to CLL progression is
not well understood.*

clinicalomics.com

This gene has been thoroughly studied with traditional
short-read sequencing technologies, which have allowed the
identification of aberrant splicing across the transcriptome
associated with SF3B1 mutations.
Many groups have found a disproportional increase in
aberrant intron 3'-end splicing associated with these
mutations. Tang points to data from Catherine Wu's lab at
Dana-Farber Cancer Institute, with whom they are collaborating. A 2016 publication from Wu's group reported
transcriptomic characterization, using short reads, of
primary CLL cells to identify transcripts and pathways
affected by SF3B1 mutations. They found a much greater
number of aberrant intron 3' splice sites than were seen
in cells with wild-type SF3B1 (Wang, L. et al. Cancer Cell
2016;30:750-763).
However, the inherent challenges of short sequencing reads
limit their application to the analysis of splice junctions alone,
rather than entire isoforms. That in turn limits understanding
of the functional consequences of these aberrant splicing
changes.

http://www.clinicalomics.com

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