Rapid selection of BRCA1-proficient tumor cells during neoadjuvant therapy for ovarian cancer in BRCA1 mutation carriers.

Autor: Sokolenko AP; Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; Department of Medical Genetics, St.-Petersburg Pediatric Medical University, St.-Petersburg 194100, Russia., Savonevich EL; Department of Obstetrics and Gynecology, Grodno State Medical University, Grodno 230023, Belarus., Ivantsov AO; Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia., Raskin GA; Department of Pathology, Russian Research Centre for Radiology and Surgical Technologies, St. Petersburg 197758, Russia., Kuligina ES; Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia., Gorodnova TV; Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia., Preobrazhenskaya EV; Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia., Kleshchov MA; Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia., Tiurin VI; Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia., Mukhina MS; Department of Pathology, Russian Research Centre for Radiology and Surgical Technologies, St. Petersburg 197758, Russia., Kotiv KB; Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia., Shulga AV; Department of Obstetrics and Gynecology, Grodno State Medical University, Grodno 230023, Belarus., Kuznetsov SG; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland., Berlev IV; Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia., Imyanitov EN; Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; Department of Medical Genetics, St.-Petersburg Pediatric Medical University, St.-Petersburg 194100, Russia; Department of Medical Genetics, I.I. Mechnikov North-Western Medical University, St.-Petersburg 191015, Russia; Department of Oncology, St.-Petersburg State University, St.-Petersburg 199034, Russia. Electronic address: evgeny@imyanitov.spb.ru.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2017 Jul 01; Vol. 397, pp. 127-132. Date of Electronic Publication: 2017 Apr 01.
DOI: 10.1016/j.canlet.2017.03.036
Abstrakt: Ovarian carcinomas (OC) often demonstrate rapid tumor shrinkage upon neoadjuvant chemotherapy (NACT). However, complete pathologic responses are very rare and the mechanisms underlying the emergence of residual tumor disease remain elusive. We hypothesized that the change of somatic BRCA1 status may contribute to this process. The loss-of-heterozygosity (LOH) at the BRCA1 locus was determined for 23 paired tumor samples obtained from BRCA1 germ-line mutation carriers before and after NACT. We observed a somatic loss of the wild-type BRCA1 allele in 74% (17/23) of OCs before NACT. However, a retention of the wild-type BRCA1 copy resulting in a reversion of LOH status was detected in 65% (11/17) of those patients after NACT. Furthermore, we tested 3 of these reversion samples for LOH at intragenic BRCA1 single nucleotide polymorphisms (SNPs) and confirmed a complete restoration of the SNP heterozygosity in all instances. The neoadjuvant chemotherapy for BRCA1-associated OC is accompanied by a rapid expansion of pre-existing BRCA1-proficient tumor clones suggesting that continuation of the same therapy after NACT and surgery may not be justified even in patients initially experiencing a rapid tumor regression.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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