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Frequency and molecular characteristics of PALB2-associated cancers in Russian patients.
Preobrazhenskaya, Elena V; Shleykina, Alla U; Gorustovich, Olga A; Martianov, Alexandr S; Bizin, Ilya V; Anisimova, Elena I; Sokolova, Tatjana N; Chuinyshena, Svetlana A; Kuligina, Ekatherina Sh; Togo, Alexandr V; Belyaev, Alexey M; Ivantsov, Alexandr O; Sokolenko, Anna P; Imyanitov, Evgeny N.
Afiliación
  • Preobrazhenskaya EV; N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
  • Shleykina AU; St. Petersburg Pediatric Medical University, St. Petersburg, Russia.
  • Gorustovich OA; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Federal Research and Clinical Center of Physical and Chemical Medicine, Moscow, Russia.
  • Martianov AS; N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
  • Bizin IV; N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
  • Anisimova EI; St. Petersburg Pediatric Medical University, St. Petersburg, Russia.
  • Sokolova TN; N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
  • Chuinyshena SA; St. Petersburg Regional Cancer Hospital, St. Petersburg, Russia.
  • Kuligina ES; N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
  • Togo AV; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Federal Research and Clinical Center of Physical and Chemical Medicine, Moscow, Russia.
  • Belyaev AM; St. Petersburg Pediatric Medical University, St. Petersburg, Russia.
  • Ivantsov AO; N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
  • Sokolenko AP; St. Petersburg Pediatric Medical University, St. Petersburg, Russia.
  • Imyanitov EN; N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
Int J Cancer ; 148(1): 203-210, 2021 01 01.
Article en En | MEDLINE | ID: mdl-32997802
PALB2 is а high-penetrance gene for hereditary breast cancer (BC). Our study aimed to investigate the spectrum of PALB2 mutations in Russian cancer patients. PALB2 sequencing revealed pathogenic variants in 3/190 (1.6%) young-onset and/or familial and/or bilateral BC cases but none in 96 ovarian cancer (OC) or 172 pancreatic cancer patients. Subsequently, seven recurrent PALB2 pathogenic alleles were selected from this and previous Slavic studies and tested in an extended patient series. PALB2 pathogenic variants were detected in 5/585 (0.9%) "high-risk" BC, 10/1508 (0.7%) consecutive BC and 5/1802 (0.3%) OC cases. Haplotyping suggested that subjects with Slavic alleles c.509-510delGA (n = 10) and c.172-175delTTGT (n = 4) as well as carriers of Finnish c.1592delT mutation (n = 4) originated from a single founder each, while PALB2 p.R414X allele (n = 4) had at least two independent founders. Somatic loss of heterozygosity (LOH) was revealed in 5/10 chemonaive BCs and in 0/2 BC samples obtained after neoadjuvant therapy. Multigene sequencing identified somatic PALB2 inactivating point mutation in one out of two tumors without PALB2 LOH but in none of four BCs with PALB2 LOH. Genomic instability, as determined by NGS, was observed in four out of five tumors with biallelic PALB2 inactivation but not in the BC sample with the preserved wild-type PALB2 allele. PALB2 germ-line mutations contribute to a small fraction of cancer cases in Russia. The majority although not all PALB2-driven BCs have somatic inactivation of the remaining PALB2 allele and therefore potential sensitivity to platinum compounds and PARP inhibitors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Carcinoma / Predisposición Genética a la Enfermedad / Proteína del Grupo de Complementación N de la Anemia de Fanconi Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia / Europa Idioma: En Revista: Int J Cancer Año: 2021 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Carcinoma / Predisposición Genética a la Enfermedad / Proteína del Grupo de Complementación N de la Anemia de Fanconi Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia / Europa Idioma: En Revista: Int J Cancer Año: 2021 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Estados Unidos