Page 28 - Read Online

J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108 Page 23 of 27

globalized, i.e., delocalized to countries that do not have the means to ensure (universal) access to high-cost
medicines. Although substantial numbers of anti-cancer medicines are nowadays included in national lists
of LMICs, their affordability and accessibility at country-level are often far from ensured. The relevance of
benefit sharing in international research is still poorly understood. A legal framework formulating benefit-
sharing requirements in international research is necessary.

31. TP53 analysis in hematological malignancies

Ahad A. Kodipad, Silvia Rasi, Clara Deambrogi, Simone Favini, Denise Peroni, Sruthi Sagiraju,
Ramesh Adhinaveni, Sreekar Kogila, Fary Diop, Chiara Favini, Riccardo Moia, Lorenzo De
Paoli, Gloria Margiotta Casaluci, Elena Crisà, Andrea Patriarca, Gianluca Gaidano

Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern
Piedmont, Novara 28100, Italy.

Introduction: Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in
the Western World. TP53 disruption (e.g., 17p del and/or TP53 mutations) is associated with chemo-
refractoriness and is now used in the clinical practice as a predictive biomarker. Moreover, also in
myelodysplastic syndrome (MDS) TP53 seems to be associated with an inferior outcome. Based on these
observations, the objective of the project is to characterize TP53 mutations in a prospective cohort of CLL
and MDS patients to better define the frequency and the clinical implications of TP53 mutations.

Experimental model: The study is based on the analysis of 53 CLL and 26 MDS patients. The mutational
analysis of the TP53 gene was performed using genomic DNA extracted from tumor cells. Peripheral blood
was collected for CLL patients, while bone marrow for MDS patients. The TP53 gene was analyzed by Sanger
sequencing from exons 2 to 11.

Results: In the CLL group 5/53 (9.4%) cases showed TP53 mutation. All mutations were missense and were
reported in the IARC database. All TP53 mutations predicted functional consequences and were all reported
as pathogenic mutations. At diagnosis, TP53 mutations associated with advanced age (P = 0.031), advanced
Binet stage (P = 0.021) and higher β2-microglobulin levels (P = 0.018). In MDS 2/26 (7.7%) patients harbored
TP53 mutation. These two mutations were missense and were validated by the IARC database. Both of TP53
mutated patients were treated with azacitidine but progressed early after treatment start.

Conclusion: In this prospective CLL cohort, TP53 mutations reflect the mutation profile already reported,
with the novel finding of the correlation between TP53 and higher β2-microglobulin levels. In MDS, TP53
seems to be associated with an advance disease and with early progression after therapy. Longer follow up is
needed for univariate and multivariate survival analysis stratified according to TP53 mutations.

32. Epigenetic changes in ovarian cancer cells subjected to starvation or to the caloric

restriction mimetic Resveratrol

1
1
1
2
Letizia Vallino , Alessandra Ferraresi , Chiara Vidoni , Claudia Lora, Giovanna Chiorino ,
Alessandra Galetto , Ciro Isidoro 1
3
1 Laboratory of Molecular Pathology, Department of Health Sciences, Università del Piemonte Orientale “A.
Avogadro”, Via Solaroli 17, Novara 28100, Italy.