TY - JOUR
T1 - Targeted locus amplification to detect molecular markers in mantle cell and follicular lymphoma
AU - Genuardi, Elisa
AU - Klous, Petra
AU - Mantoan, Barbara
AU - Drandi, Daniela
AU - Ferrante, Martina
AU - Cavallo, Federica
AU - Alessandria, Beatrice
AU - Dogliotti, Irene
AU - Grimaldi, Daniele
AU - Ragaini, Simone
AU - Clerico, Michele
AU - Lo Schirico, Mariella
AU - Saraci, Elona
AU - Yilmaz, Mehmet
AU - Zaccaria, Gian Maria
AU - Cortelazzo, Sergio
AU - Vitolo, Umberto
AU - Luminari, Stefano
AU - Federico, Massimo
AU - Boccadoro, Mario
AU - van Min, Max
AU - Splinter, Erik
AU - Ladetto, Marco
AU - Ferrero, Simone
N1 - Funding Information:
This work was supported by: Fondi di Ricerca Locale, Università degli Studi di Torino, Italy; Fondazione Neoplasie Del Sangue (Fo.Ne.Sa), Torino, Italy; Fondazione CRT (projects code: 2016.0677, 2018.1284), Torino, Italy; Fondazione Da Rosa, Torino, Italy; Young Researcher Award 2018 by Fondazione Italiana Linfomi (FIL), Fondazione Giulia Maramotti and Fondazione Grade ONLUS, Reggio Emilia, Italy; Cancer Research UK [C355/A26819] and FC AECC and AIRC.
Publisher Copyright:
© 2021 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.
PY - 2021/8
Y1 - 2021/8
N2 - Minimal residual disease (MRD) monitoring by PCR methods is a strong and standardized predictor of clinical outcome in mantle cell lymphoma (MCL) and follicular lymphoma (FL). However, about 20% of MCL and 40% of FL patients lack a reliable molecular marker, being thus not eligible for MRD studies. Recently, targeted locus amplification (TLA), a next-generation sequencing (NGS) method based on the physical proximity of DNA sequences for target selection, identified novel gene rearrangements in leukemia. The aim of this study was to test TLA in MCL and FL diagnostic samples lacking a classical, PCR-detectable, t(11; 14) MTC (BCL1/IGH), or t(14; 18) major breakpoint region and minor cluster region (BCL2/IGH) rearrangements. Overall, TLA was performed on 20 MCL bone marrow (BM) or peripheral blood (PB) primary samples and on 20 FL BM, identifying a novel BCL1 or BCL2/IGH breakpoint in 16 MCL and 8 FL patients (80% and 40%, respectively). These new breakpoints (named BCL1-TLA and BCL2-TLA) were validated by ASO primers design and compared as MRD markers to classical IGH rearrangements in eight MCL: overall, MRD results by BCL1-TLA were superimposable (R Pearson = 0.76) to the standardized IGH-based approach. Moreover, MRD by BCL2-TLA reached good sensitivity levels also in FL and was predictive of a primary refractory case. In conclusion, this study offers the proof of principle that TLA is a promising and reliable NGS-based technology for the identification of novel molecular markers, suitable for further MRD analysis in previously not traceable MCL and FL patients.
AB - Minimal residual disease (MRD) monitoring by PCR methods is a strong and standardized predictor of clinical outcome in mantle cell lymphoma (MCL) and follicular lymphoma (FL). However, about 20% of MCL and 40% of FL patients lack a reliable molecular marker, being thus not eligible for MRD studies. Recently, targeted locus amplification (TLA), a next-generation sequencing (NGS) method based on the physical proximity of DNA sequences for target selection, identified novel gene rearrangements in leukemia. The aim of this study was to test TLA in MCL and FL diagnostic samples lacking a classical, PCR-detectable, t(11; 14) MTC (BCL1/IGH), or t(14; 18) major breakpoint region and minor cluster region (BCL2/IGH) rearrangements. Overall, TLA was performed on 20 MCL bone marrow (BM) or peripheral blood (PB) primary samples and on 20 FL BM, identifying a novel BCL1 or BCL2/IGH breakpoint in 16 MCL and 8 FL patients (80% and 40%, respectively). These new breakpoints (named BCL1-TLA and BCL2-TLA) were validated by ASO primers design and compared as MRD markers to classical IGH rearrangements in eight MCL: overall, MRD results by BCL1-TLA were superimposable (R Pearson = 0.76) to the standardized IGH-based approach. Moreover, MRD by BCL2-TLA reached good sensitivity levels also in FL and was predictive of a primary refractory case. In conclusion, this study offers the proof of principle that TLA is a promising and reliable NGS-based technology for the identification of novel molecular markers, suitable for further MRD analysis in previously not traceable MCL and FL patients.
KW - follicular lymphoma
KW - mantle cell lymphoma
KW - marker screening
KW - minimal residual disease
KW - NGS
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U2 - 10.1002/hon.2864
DO - 10.1002/hon.2864
M3 - Article
C2 - 33742718
AN - SCOPUS:85103388808
VL - 39
SP - 293
EP - 303
JO - Hematological Oncology
JF - Hematological Oncology
SN - 0278-0232
IS - 3
ER -