Abstract 4136: Mutational analysis of paired primary and relapse diffuse large B-cell lymphoma
Authors: Juskevicius Darius , Perrina Valeria , Quagliatta Luca , Ruiz Christian , Dirnhofer Stephan , Tzankov Alexandar 
Published: August 2015

Recurrences of diffuse large b-cell lymphoma (DLBCL) represent a high risk of worse outcome, however knowledge on the genetic mechanism of such relapses is still lacking. In general, recurrences are considered to be outgrowths of the original neoplasm, but this concept has been challenged by rare demonstration of clonally unrelated. In our previous study we analyzed chromosomal copy number aberrations in paired primary-relapse DLBCL samples and demonstrated the existence of three different modes of tumor evolution: (i) clonally unrelated relapses, (ii) clonally related relapses via a putative common progenitor (branching evolution) and (iii) clonally related relapses with linear progression. In the current continuation study we aimed to validate our previous findings and to expand the dataset by identifying mutations in genes reported to be frequently mutated in lymphomas at primary and relapse stages of paired DLBCL samples. In addition, we compare the obtained results to the mutational profile of DLBCL that never relapsed.

We designed and validated a multiplex PCR-based target-enrichment panel for the 30 most frequently affected genes in lymphomas. Target-enriched libraries were constructed using the genomic DNA of 25 matched primary-relapse pairs as well as 20 non-relapsing DLBCL samples. Sequencing was performed with the IonTorrent PGM sequencer.

The data collection is currently in progress. Mutational data of the paired primary and relapse samples of DLBCL will allow us to identify DNA mutations which occur early at the primary stage and are most probably associated with disease onset. Mutations that occur at relapse will also be detected, allowing insight into genetic mechanisms that lead to DLBCL recurrence. Chromosomal aberration data available for the majority of those samples will assist the more precise interpretation of mutated allelic fractions and a holistic approach to the analysis of the affected regulatory pathways.

Lack of knowledge on the genetic mechanisms of DLBCL relapse exists despite the fact that these recurrences are the main cause of morbidity and mortality in such patients. Paired sample analysis gives a unique opportunity for an insight in this field. Earlier, analyzing paired primary-relapse samples, we provided clear evidence for the existence of clonally unrelated relapses as well as different genetic patterns of DLBCL recurrence. The current study will complete the characterization of the paired DLBCL cohort at the base-pair resolution allowing identification of mutations occurring early at the onset and relapse stages of the disease.

Citation Format: Darius Juskevicius, Valeria Perrina, Luca Quagliatta, Christian Ruiz, Stephan Dirnhofer, Alexandar Tzankov. Mutational analysis of paired primary and relapse diffuse large B-cell lymphoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4136. doi:10.1158/1538-7445.AM2015-4136