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academies
Case Reports in Surgery and Invasive Procedures | Volume 3
March 11-12, 2019 | London, UK
Biomarkers
Plastic and Cosmetic Surgery
International Conference on
International Conference on
Joint Event
&
Biological and genetic factors associated to treatment resistance in lymphoma
Ken H Young
The University of Texas, USA
D
iffuse large B cell lymphoma (DLBCL) is the most common
type of lymphoma and accounts for 30% - 40% of all
non-Hodgkin lymphomas. In the past two decades, results
from several phase 3 studies have established the rituximab,
cyclophosphamide, doxorubicin, vincristine, and prednisone
(R-CHOP) as the standard therapy for patients with DLBCL with
50-70% of patients being cured. The remaining patients are
refractory to R-CHOP or relapse after complete response (CR).
Understanding the biology of DLBCL is essential for identifying
patients who are not cured by R-CHOP and uncovering potential
pathways that could be targeted. A milestone in the research
of DLBCL biology is the identification of two different subtypes
of DLBCL, germinal center B-like (GCB) and activated B-like
(ABC). These two types of DLBCL show distinct gene expression
profiles and different clinical outcomes. With the advent of high-
throughput sequencing platforms, an increasing number of
driver genes in the pathogenesis of DLBCL have been unveiled.
Recently, three studies comprising over 1800 DLBCL cases
were assessed using whole-exome sequencing with other
high-throughput techniques to comprehensively define the
genomic landscape of DLBCL, providing more insights into DLBCL
development and potential therapeutic targets. I will present the
prevalence, functional roles, and clinical implications of genetic
events including somatic mutations, copy number alterations
(CNVs), and chromosomal translocations in DLBCL.
Clinical heterogeneity is a major challenge for the treatment
of DLBCL. Different cell-of-origin may contribute to the distinct
biology of DLBCL as suggested by the germinal center-like
and activated B cell (ABC)-like DLBCL classification system.
Characterization of biological and genetic parameters underlying
the molecular mechanisms help to identify critical targets
responsible for drug resistance, treatment failure and recurrence,
and it is helpful for better understanding the pathogenesis
of DLBCL. In this presentation, the important molecular and
biological events are systemically analyzed in a large cohort of de
novo DLBCL patients to evaluate for the correlation of biological
and genetic parameters with clinical outcome using high-
throughput next generation sequencing (NGS). Gene expression
and epigenetic miRNA profiling have also been explored for
particular signature from each of the patients based on B-cell
differentiation. Combined genetic, clinical and pathologic
dissections provide insight in better understanding of the cell-of-
origin, drug resistance, and recurrence in DLBCL patients.
The elaboration of the genetics of DLBCL not only improves our
understanding of disease pathogenesis, but also provides us
with insights about disease classification, prognostication and
therapeutic targets.
e:
khyoung@mdanderson.org