| Title: |
Rapid selection of BRCA1-proficient tumor cells during neoadjuvant therapy for ovarian cancer in BRCA1 mutation carriers |
| Authors: |
Sokolenko, Anna P.; Savonevich, Elena L.; Ivantsov, Alexandr O.; Raskin, Grigory A.; Kuligina, Ekatherina S.; Gorodnova, Tatiana V.; Preobrazhenskaya, Elena V.; Kleshchov, Maxim A.; Tiurin, Vladislav I.; Mukhina, Marina S.; Kotiv, Khristina B.; Shulga, Andrey V.; Kuznetsov, Sergey G.; Berlev, Igor V.; Imyanitov, Evgeny N. |
| Contributors: |
Institute for Molecular Medicine Finland; Sergey Kuznetsov / Principal Investigator |
| Publisher Information: |
Elsevier Ireland Ltd. |
| Publication Year: |
2018 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
BRCA1; Ovarian cancer; Neoadjuvant therapy; Loss-of-heterozygosity; Treatment resistance; PRIMARY SURGERY; BREAST-CANCER; FOUNDER MUTATIONS; CHEMOTHERAPY; RESISTANCE; PROTEIN; PROGRESSION; CARCINOMAS; Cancers |
| Description: |
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 BRCAI 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 BRCA1single 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. (C) 2017 Elsevier B.V. All rights reserved. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Patient selection and clinical analysis is supported by the Russian Scientific Fund [grant number 14-25-00111]. Tissue analysis is supported by the Russian and Belorussian Foundations for Basic Research [grant number 16-54-00055/M16P-214].; https://hdl.handle.net/10138/235610; 85017435392; 000401382000014 |
| Availability: |
https://hdl.handle.net/10138/235610 |
| Rights: |
unspecified ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.4AC8CBB7 |
| Database: |
BASE |