title: PALB2- Ð°ÑÑÐ¾ÑÐ¸Ð¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÐ¹ ÑÐ°Ðº: ÑÐ°ÑÑÐ¾ÑÐ° Ð¼ÑÑÐ°ÑÐ¸Ð¹, ÐºÐ»Ð¸Ð½Ð¸ÐºÐ¾-Ð¼Ð¾ÑÑÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ðµ Ð¾ÑÐ¾Ð±ÐµÐ½Ð½Ð¾ÑÑÐ¸, "ÑÑÑÐµÐºÑ Ð¾ÑÐ½Ð¾Ð²Ð°ÑÐµÐ»Ñ"
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¼Ð°Ð³Ð¸ÑÑÑÐ°
titleType: Subtitle
title: PALB2-associated cancer: mutation rate, clinical and morphological features, "founder effect"
Creators: name: Ð¨Ð»ÐµÐ¹ÐºÐ¸Ð½Ð°, ÐÐ»Ð»Ð°
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2021
Subjects: ÐÐ¸Ð¾ÑÐµÑ Ð½Ð¾Ð»Ð¾Ð³Ð¸Ñ
ÐÐ»ÐµÑÐºÐ° (Ð±Ð¸Ð¾Ð».)
Ð½Ð°ÑÐ»ÐµÐ´ÑÑÐ²ÐµÐ½Ð½ÑÐ¹ ÑÐ°Ðº Ð¼Ð¾Ð»Ð¾ÑÐ½Ð¾Ð¹ Ð¶ÐµÐ»ÐµÐ·Ñ
Ð¼ÑÑÐ°ÑÐ¸Ñ
hereditary breast cancer
mutation

description: PALB2 (Ð¿Ð°ÑÑÐ½ÐµÑ Ð¸ Ð»Ð¾ÐºÐ°Ð»Ð¸Ð·Ð°ÑÐ¾Ñ BRCA2) - ÑÑÐ¾ Ð³ÐµÐ½ Ð²ÑÑÐ¾ÐºÐ¾Ð¹ Ð¿ÐµÐ½ÐµÑÑÐ°Ð½ÑÐ½Ð¾ÑÑÐ¸ Ð´Ð»Ñ Ð½Ð°ÑÐ»ÐµÐ´ÑÑÐ²ÐµÐ½Ð½Ð¾Ð³Ð¾ ÑÐ°ÐºÐ° Ð¼Ð¾Ð»Ð¾ÑÐ½Ð¾Ð¹ Ð¶ÐµÐ»ÐµÐ·Ñ (Ð ÐÐ). Ð¦ÐµÐ»ÑÑ Ð½Ð°ÑÐµÐ³Ð¾ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ Ð±ÑÐ»Ð¾ Ð¸Ð·ÑÑÐµÐ½Ð¸Ðµ ÑÐ¿ÐµÐºÑÑÐ° Ð¼ÑÑÐ°ÑÐ¸Ð¹ PALB2 Ñ ÑÐ¾ÑÑÐ¸Ð¹ÑÐºÐ¸Ñ Ð¾Ð½ÐºÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ñ Ð±Ð¾Ð»ÑÐ½ÑÑ. Ð¡ÐµÐºÐ²ÐµÐ½Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ PALB2 Ð²ÑÑÐ²Ð¸Ð»Ð¾ Ð¿Ð°ÑÐ¾Ð³ÐµÐ½Ð½ÑÐµ Ð²Ð°ÑÐ¸Ð°Ð½ÑÑ Ð² 3/190 (1,6%) ÑÐ»ÑÑÐ°ÑÑ Ð ÐÐ Â«Ð²ÑÑÐ¾ÐºÐ¾Ð³Ð¾ ÑÐ¸ÑÐºÐ°Â» (Ð¼Ð¾Ð»Ð¾Ð´ÑÑ Ð¸/Ð¸Ð»Ð¸ ÑÐµÐ¼ÐµÐ¹Ð½ÑÑ Ð¸/Ð¸Ð»Ð¸ Ð±Ð¸Ð»Ð°ÑÐµÑÐ°Ð»ÑÐ½ÑÑ), Ð½Ð¾ Ð½Ð¸ Ð¾Ð´Ð½Ð¾Ð³Ð¾ Ñ 96 Ð±Ð¾Ð»ÑÐ½ÑÑ ÑÐ°ÐºÐ¾Ð¼ ÑÐ¸ÑÐ½Ð¸ÐºÐ¾Ð² (Ð Ð¯) Ð¸Ð»Ð¸ 172 Ð±Ð¾Ð»ÑÐ½ÑÑ ÑÐ°ÐºÐ¾Ð¼ Ð¿Ð¾Ð´Ð¶ÐµÐ»ÑÐ´Ð¾ÑÐ½Ð¾Ð¹ Ð¶ÐµÐ»ÐµÐ·Ñ. ÐÐ¿Ð¾ÑÐ»ÐµÐ´ÑÑÐ²Ð¸Ð¸ ÑÐµÐ¼Ñ Ð¿Ð¾Ð²ÑÐ¾ÑÑÑÑÐ¸ÑÑÑ Ð¿Ð°ÑÐ¾Ð³ÐµÐ½Ð½ÑÑ Ð°Ð»Ð»ÐµÐ»ÐµÐ¹ PALB2 Ð±ÑÐ»Ð¸ Ð¾ÑÐ¾Ð±ÑÐ°Ð½Ñ Ð¸Ð· ÑÑÐ¾Ð³Ð¾ Ð¸ Ð¿ÑÐµÐ´ÑÐ´ÑÑÐ¸Ñ ÑÐ»Ð°Ð²ÑÐ½ÑÐºÐ¸Ñ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ð¹ Ð¸ Ð¿ÑÐ¾ÑÐµÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ñ Ð² ÑÐ°ÑÑÐ¸ÑÐµÐ½Ð½Ð¾Ð¹ ÑÐµÑÐ¸Ð¸ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð². ÐÐ°ÑÐ¾Ð³ÐµÐ½Ð½ÑÐµ Ð²Ð°ÑÐ¸Ð°Ð½ÑÑ PALB2 Ð±ÑÐ»Ð¸ Ð¾Ð±Ð½Ð°ÑÑÐ¶ÐµÐ½Ñ Ð² 5/585 (0,9%) Ð ÐÐ Â«Ð²ÑÑÐ¾ÐºÐ¾Ð³Ð¾ ÑÐ¸ÑÐºÐ°Â», 10/1508 (0,7%) Ð¿Ð¾ÑÐ»ÐµÐ´Ð¾Ð²Ð°ÑÐµÐ»ÑÐ½ÑÑ Ð ÐÐ Ð¸ 5/1802 (0,3%) ÑÐ»ÑÑÐ°ÑÑ ÑÐ°ÐºÐ° ÑÐ¸ÑÐ½Ð¸ÐºÐ° (Ð Ð¯). ÐÐ°Ð¿Ð»Ð¾ÑÐ¸Ð¿Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ Ð°Ð»Ð»ÐµÐ»ÑÐ¼Ð¸: c.509-510delGA (n = 10) Ð¸ c.172-175delTTGT (n = 4), Ð° ÑÐ°ÐºÐ¶Ðµ Ð½Ð¾ÑÐ¸ÑÐµÐ»ÐµÐ¹ ÑÐ¸Ð½ÑÐºÐ¾Ð¹ Ð¼ÑÑÐ°ÑÐ¸Ð¸ c.1592delT (n = 4) Ð¿Ð¾ÐºÐ°Ð·Ð°Ð»Ð¾ Ð¿ÑÐ¾Ð¸ÑÑÐ¾Ð¶Ð´ÐµÐ½Ð¸Ðµ Ð¾Ñ ÐµÐ´Ð¸Ð½Ð¾Ð³Ð¾ Â«Ð¾ÑÐ½Ð¾Ð²Ð°ÑÐµÐ»ÑÂ» Ð´Ð»Ñ ÐºÐ°Ð¶Ð´Ð¾Ð¹ Ð¼ÑÑÐ°ÑÐ¸Ð¸, Ð² ÑÐ¾ Ð²ÑÐµÐ¼Ñ ÐºÐ°Ðº Ð°Ð»Ð»ÐµÐ»Ñ PALB2 p.R414X (n = 4) Ð¸Ð¼ÐµÐ», Ð¿Ð¾ ÐºÑÐ°Ð¹Ð½ÐµÐ¹ Ð¼ÐµÑÐµ, Ð´Ð²ÑÑ Ð½ÐµÐ·Ð°Ð²Ð¸ÑÐ¸Ð¼ÑÑ Â«Ð¾ÑÐ½Ð¾Ð²Ð°ÑÐµÐ»ÐµÐ¹Â». Ð¡Ð¾Ð¼Ð°ÑÐ¸ÑÐµÑÐºÐ°Ñ Ð¿Ð¾ÑÐµÑÑ Ð³ÐµÑÐµÑÐ¾Ð·Ð¸Ð³Ð¾ÑÐ½Ð¾ÑÑÐ¸ (LOH) Ð±ÑÐ»Ð° Ð²ÑÑÐ²Ð»ÐµÐ½Ð° Ð² 5/10 ÑÐµÐ¼Ð¾Ð½Ð°Ð¸Ð²Ð½ÑÑ Ð ÐÐ Ð¸ Ð² 0/2 Ð¾Ð±ÑÐ°Ð·ÑÐ°Ñ Ð ÐÐ, Ð¿Ð¾Ð»ÑÑÐµÐ½Ð½ÑÑ Ð¿Ð¾ÑÐ»Ðµ Ð½ÐµÐ¾Ð°Ð´ÑÑÐ²Ð°Ð½ÑÐ½Ð¾Ð¹ ÑÐµÑÐ°Ð¿Ð¸Ð¸. ÐÐ°ÑÐ»ÐµÐ´ÑÑÐ²ÐµÐ½Ð½ÑÐµ Ð¼ÑÑÐ°ÑÐ¸Ð¸ PALB2 Ð²Ð½Ð¾ÑÑÑ ÑÐ²Ð¾Ð¹ Ð²ÐºÐ»Ð°Ð´ Ð² Ð½ÐµÐ±Ð¾Ð»ÑÑÑÑ Ð´Ð¾Ð»Ñ ÑÐ»ÑÑÐ°ÐµÐ² ÑÐ°ÐºÐ° Ð² Ð Ð¾ÑÑÐ¸Ð¸. ÐÐ¾Ð»ÑÑÐ¸Ð½ÑÑÐ²Ð¾, ÑÐ¾ÑÑ Ð¸ Ð½Ðµ Ð²ÑÐµ Ð ÐÐ, Ð°ÑÑÐ¾ÑÐ¸Ð¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÐµ Ñ PALB2, Ð¸Ð¼ÐµÑÑ ÑÐ¾Ð¼Ð°ÑÐ¸ÑÐµÑÐºÑÑ Ð¸Ð½Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ñ Ð¾ÑÑÐ°Ð²ÑÐµÐ³Ð¾ÑÑ Ð°Ð»Ð»ÐµÐ»Ñ PALB2 Ð¸, ÑÐ»ÐµÐ´Ð¾Ð²Ð°ÑÐµÐ»ÑÐ½Ð¾, Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»ÑÐ½ÑÑ ÑÑÐ²ÑÑÐ²Ð¸ÑÐµÐ»ÑÐ½Ð¾ÑÑÑ Ðº ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸ÑÐ¼ Ð¿Ð»Ð°ÑÐ¸Ð½Ñ Ð¸ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾ÑÐ°Ð¼ PARP.
description: PALB2 (Partner and Localizer of BRCA2) is a highly penetrant gene for hereditary breast cancer (BC). The aim of our study was to study the spectrum of PALB2 mutations in Russian cancer patients. PALB2 sequencing revealed pathogenic variants in 3/190 (1.6%) young and/or familial and/or bilateral breast cancer cases, but none in 96 ovarian cancer patients or 172 pancreatic cancer patients. Subsequently, seven recurrent pathogenic PALB2 alleles were selected from this and previous Slavic studies and tested in an extended patient series. Pathogenic variants of PALB2 were found in 5/585 (0.9%) âhigh-riskâ breast cancers, 10/1508 (0.7%) consecutive breast cancers, and 5/1802 (0.3%) breast cancers. Haplotyping showed that subjects with the Slavic alleles c. 509-510delGA (n = 10) and c.172-175delTTGT (n = 4), as well as carriers of the Finnish mutation c.1592delT (n = 4), descended from one founder each, while the PALB2 allele p.R414X (n = 4) had at least two independent founders. Somatic loss of heterozygosity (LOH) was detected in 5/10 chemonaive breast cancer and in 0/2 breast cancer samples obtained after neoadjuvant therapy. PALB2 germ line mutations contribute to a small proportion of cancer cases in Russia. Most, though not all, PALB2-controlled breast cancers have somatic inactivation of the remaining PALB2 allele and therefore potential sensitivity to platinum compounds and PARP inhibitors.