Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas
Bobillo, Sabela (Vall d'Hebron Institut d'Oncologia)
Crespo, Marta (Vall d'Hebron Institut d'Oncologia)
Escudero, Laura (Vall d'Hebron Institut d'Oncologia)
Mayor, Regina (Hospital Universitari Vall d'Hebron)
Raheja, Priyanka (Vall d'Hebron Institut d'Oncologia)
Carpio Segura, Cecilia del Carmen (Vall d'Hebron Institut d'Oncologia)
Rubio-Perez, Carlota (Vall d'Hebron Institut d'Oncologia)
Tazon-Vega, Barbara
Palacio-García, Carles (Vall d'Hebron Institut d'Oncologia)
Carabia, Júlia (Vall d'Hebron Institut d'Oncologia)
Jimenez, Isabel (Vall d'Hebron Institut d'Oncologia)
Nieto Sáchica, Juan Camilo (Vall d'Hebron Institut d'Oncologia)
Montoro Gómez, Julia (Vall d'Hebron Institut d'Oncologia)
Martinez-Ricarte, Francisco (Hospital Universitari Vall d'Hebron)
Castellvi, Josep (Hospital Universitari Vall d'Hebron)
Simo, Marc (Hospital Universitari Vall d'Hebron)
Puigdefabregas, Lluis (Vall d'Hebron Institut d'Oncologia)
Abrisqueta, Pau (Vall d'Hebron Institut d'Oncologia)
Bosch José, Francesc Xavier 1947- (Vall d'Hebron Institut d'Oncologia)
Seoane Suárez, Joan (Vall d'Hebron Institut d'Oncologia)
Universitat Autònoma de Barcelona

Fecha:	2020
Resumen:	The levels of cell free circulating tumor DNA (ctDNA) in plasma correlate with treatment response and outcome in systemic lymphomas. Notably, in brain tumors, the levels of ctDNA in the cerebrospinal fluid (CSF) are higher than in plasma. Nevertheless, their role in central nervous system (CNS) lymphomas remains elusive. We evaluated the CSF and plasma from 19 patients: 6 restricted CNS lymphomas, 1 systemic and CNS lymphoma, and 12 systemic lymphomas. We performed whole exome sequencing or targeted sequencing to identify somatic mutations of the primary tumor, then variant-specific droplet digital polymerase chain reaction was designed for each mutation. At time of enrollment, we found ctDNA in the CSF of all patients with restricted CNS lymphoma but not in patients with systemic lymphoma without CNS involvement. Conversely, plasma ctDNA was detected in only 2 out of 6 patients with restricted CNS lymphoma with lower variant allele frequencies than CSF ctDNA. Moreover, we detected CSF ctDNA in one patient with CNS lymphoma in complete remission and in one patient with systemic lymphoma, 3 and 8 months before CNS relapse was confirmed, indicating that CSF ctDNA might detect CNS relapse earlier than conventional methods. Finally, in two cases with CNS lymphoma, CSF ctDNA was still detected after treatment even though no tumoral cells were observed by flow cytometry (FC), indicating that CSF ctDNA detected residual disease better than FC. In conclusion, CSF ctDNA can detect CNS lesions better than plasma ctDNA and FC. In addition, CSF ctDNA predicted CNS relapse in CNS and systemic lymphomas.
Ayudas:	Instituto de Salud Carlos III PI16/01278 Instituto de Salud Carlos III PI17/00950 Instituto de Salud Carlos III PI17/00943 Ministerio de Ciencia e Innovación RYC-2012-12018
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Haematologica, Vol. 106 (february 2020) , p. 513-521, ISSN 1592-8721

DOI: 10.3324/haematol.2019.241208
PMID: 32079701

9 p, 6.7 MB

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