title: Ð Ð°Ð·ÑÐ°Ð±Ð¾ÑÐºÐ° ÑÐºÑÐ¸Ð½Ð¸Ð½Ð³Ð¾Ð²Ð¾Ð³Ð¾ Ð¼ÐµÑÐ¾Ð´Ð° Ð´Ð»Ñ Ð²ÑÑÐ²Ð»ÐµÐ½Ð¸Ñ Ð´ÐµÑÐ¸ÑÐ¸ÑÐ° ÑÐµÐ¿Ð°ÑÐ°ÑÐ¸Ð¸ Ð¿Ð¾ ÑÐ¸Ð¿Ñ Ð³Ð¾Ð¼Ð¾Ð»Ð¾Ð³Ð¸ÑÐ½Ð¾Ð¹ ÑÐµÐºÐ¾Ð¼Ð±Ð¸Ð½Ð°ÑÐ¸Ð¸
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: Development of a screening technique to detect homologous recombination repair deficiency
Creators: name: ÐÐ°Ð³ÑÐµÐ±Ð¸Ð½, Ð¤ÑÐ´Ð¾Ñ
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: 2023
Subjects: ÑÐ°Ðº ÑÐ¸ÑÐ½Ð¸ÐºÐ¾Ð²
Ð´ÐµÑÐ¸ÑÐ¸Ñ ÑÐµÐ¿Ð°ÑÐ°ÑÐ¸Ð¸ Ð³Ð¾Ð¼Ð¾Ð»Ð¾Ð³Ð¸ÑÐ½Ð¾Ð¹ ÑÐµÐºÐ¾Ð¼Ð±Ð¸Ð½Ð°ÑÐ¸ÐµÐ¹
ÑÐ¸ÑÑÐ¾Ð²Ð°Ñ ÐºÐ°Ð¿ÐµÐ»ÑÐ½Ð°Ñ ÐÐ¦Ð
ÑÐµÐºÐ²ÐµÐ½Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ Ð½Ð¾Ð²Ð¾Ð³Ð¾ Ð¿Ð¾ÐºÐ¾Ð»ÐµÐ½Ð¸Ñ
Ñ ÑÐ¾Ð¼Ð¾ÑÐ¾Ð¼Ð½Ð°Ñ Ð½ÐµÑÑÐ°Ð±Ð¸Ð»ÑÐ½Ð¾ÑÑÑ
ovarian cancer
homologous recombination repair deficiency
digital droplet PCR
next-generation sequencing
chromosomal instability

description: ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° ÑÐ°Ð·ÑÐ°Ð±Ð¾ÑÐºÐµ ÑÐºÑÐ¸Ð½Ð¸Ð½Ð³Ð¾Ð²Ð¾Ð¹ Ð¼ÐµÑÐ¾Ð´Ð¸ÐºÐ¸, ÑÐ¿Ð¾ÑÐ¾Ð±-Ð½Ð¾Ð¹ Ð²ÑÑÐ²Ð»ÑÑÑ Ð´ÐµÑÐ¸ÑÐ¸Ñ ÑÐµÐ¿Ð°ÑÐ°ÑÐ¸Ð¸ Ð¿Ð¾ ÑÐ¸Ð¿Ñ Ð³Ð¾Ð¼Ð¾Ð»Ð¾Ð³Ð¸ÑÐ½Ð¾Ð¹ ÑÐµÐºÐ¾Ð¼Ð±Ð¸Ð½Ð°ÑÐ¸ÐµÐ¹ (HRD). ÐÐ° ÑÐµÐ³Ð¾Ð´Ð½ÑÑÐ½Ð¸Ð¹ Ð´ÐµÐ½Ñ Ð´Ð»Ñ Ð¾Ð¿ÑÐµÐ´ÐµÐ»ÐµÐ½Ð¸Ñ HRD-ÑÑÐ°ÑÑÑÐ° ÑÑÑÐµÑÑÐ²ÑÑÑ ÐºÑÐ°Ð¹Ð½Ðµ Ð´Ð¾ÑÐ¾Ð³Ð¾ÑÑÐ¾ÑÑÐ¸Ðµ, Ð²ÑÐµÐ¼Ñ- Ð¸ ÑÐµÑÑÑÑÐ¾Ð·Ð°ÑÑÐ°ÑÐ½ÑÐµ ÑÐµÑÑ-ÑÐ¸ÑÑÐµÐ¼Ñ Ð½Ð° Ð¾ÑÐ½Ð¾Ð²Ðµ Ð¼ÐµÑÐ¾Ð´Ð¾Ð² NGS Ð¸ MLPA. ÐÐ¾ÑÑÐ¾Ð¼Ñ ÑÐµÐ»Ñ Ð´Ð°Ð½Ð½Ð¾Ð¹ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð¾ ÑÐ¾Ð·Ð´Ð°Ð½Ð¸Ðµ Ð¼ÐµÑÐ¾Ð´Ð¸-ÐºÐ¸, ÑÐ¿Ð¾ÑÐ¾Ð±Ð½Ð¾Ð¹ Ð¿ÑÐµÐ´ÑÐºÐ°Ð·ÑÐ²Ð°ÑÑ Ð½Ð°Ð»Ð¸ÑÐ¸Ðµ HRD Ð² Ð¾Ð¿ÑÑÐ¾Ð»Ð¸ ÑÐµÐ»Ð¾Ð²ÐµÐºÐ°, Ð½Ð° Ð¾ÑÐ½Ð¾Ð²Ðµ ÑÐ¸ÑÑÐ¾Ð²Ð¾Ð¹ ÐºÐ°Ð¿ÐµÐ»ÑÐ½Ð¾Ð¹ ÐÐ¦Ð  ÐºÐ°Ðº Ð±Ð¾Ð»ÐµÐµ Ð±ÑÑÑÑÐ¾Ð³Ð¾ Ð¸ Ð´Ð¾ÑÑÑÐ¿Ð½Ð¾Ð³Ð¾ Ð¼ÐµÑÐ¾Ð´Ð°. ÐÐ»Ñ Ð´Ð¾ÑÑÐ¸Ð¶ÐµÐ½Ð¸Ñ ÑÐµÐ»Ð¸ Ñ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ BRCA-Ð°ÑÑÐ¾ÑÐ¸Ð¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÐ¼ ÑÐ°ÐºÐ¾Ð¼ ÑÐ¸ÑÐ½Ð¸ÐºÐ¾Ð² Ð±ÑÐ»Ð¸ Ð¿ÑÐ¾Ð°Ð½Ð°Ð»Ð¸Ð·Ð¸ÑÐ¾Ð²Ð°Ð½Ñ HRD-Ð¿Ð¾Ð»Ð¾Ð¶Ð¸ÑÐµÐ»ÑÐ½ÑÐµ Ð¿ÑÐ¾ÑÐ¸Ð»Ð¸ Ð¸ Ð²ÑÑÐ²Ð»ÐµÐ½Ñ Ð»Ð¾ÐºÑÑÑ, Ð² ÐºÐ¾ÑÐ¾ÑÑÑ Ð½Ð°Ð¸Ð±Ð¾Ð»ÐµÐµ ÑÐ°ÑÑÐ¾ Ð²ÑÑÑÐµÑÐ°ÐµÑÑÑ Ð½Ð°ÑÑÑÐµÐ½Ð¸Ðµ ÐºÐ¾Ð¿Ð¸Ð¹Ð½Ð¾ÑÑÐ¸. Ð¢Ð°ÐºÐ¸-Ð¼Ð¸ Â«ÑÐ¾ÑÐºÐ°Ð¼Ð¸Â» Ð¸Ð½ÑÐµÑÐµÑÐ° ÑÑÐ°Ð»Ð¸ Ð½Ð°ÑÑÑÐµÐ½Ð¸Ñ ÐºÐ¾Ð¿Ð¸Ð¹Ð½Ð¾ÑÑÐ¸ Ð² Ð»Ð¾ÐºÑÑÐ°Ñ Ð½Ð° 8, 13, 17, 19 Ð¸ 22 ÑÑÐ¾Ð¼Ð¾ÑÐ¾Ð¼Ð°Ñ, Ð² ÑÐ¾Ð¼ ÑÐ¸ÑÐ»Ðµ Ð°Ð¼Ð¿Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ñ Ð³ÐµÐ½Ð° C-MYC. ÐÐ° Ð¾ÑÐ½Ð¾Ð²Ðµ ÑÑÐ¸Ñ Ð½Ð°Ð±Ð»ÑÐ´ÐµÐ½Ð¸Ð¹ Ð±ÑÐ» ÑÐ¾Ð·Ð´Ð°Ð½ Ð´Ð¸Ð·Ð°Ð¹Ð½ Ð¼ÐµÑÐ¾Ð´Ð¸ÐºÐ¸ Ñ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°-Ð½Ð¸ÐµÐ¼ Ð¼ÐµÑÐ¾Ð´Ð° ddPCR. Ð¢Ð°ÐºÐ¶Ðµ Ð² ÑÐ¾Ð´Ðµ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð¸ Ð¾Ð¿ÑÐµÐ´ÐµÐ»ÐµÐ½Ñ ÐºÑÐ¸ÑÐµÑÐ¸Ð¸ ÑÐ¾Ð¾Ñ-Ð²ÐµÑÑÑÐ²Ð¸Ñ Ð½ÐµÑÑÐ°Ð±Ð¸Ð»ÑÐ½Ð¾ÑÑÐ¸ Ð³ÐµÐ½Ð¾Ð¼Ð°, Ð²ÑÑÐ²Ð»ÑÐµÐ¼Ð¾Ð¹ ÑÐ°Ð·ÑÐ°Ð±Ð¾ÑÐ°Ð½Ð½ÑÐ¼ ddPCR-ÑÐµÑÑÐ¾Ð¼, HRD-ÑÑÐ°ÑÑÑÑ Ð² Ð¾Ð¿ÑÑÐ¾Ð»ÐµÐ²Ð¾Ð¼ Ð¼Ð°ÑÐµÑÐ¸Ð°Ð»Ðµ. Ð Ð¿ÑÐ¾ÑÐµÑÑÐµ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð¾ Ð¿Ð¾ÐºÐ°Ð·Ð°Ð½Ð¾, ÑÑÐ¾ ÑÐ°Ð·ÑÐ°Ð±Ð¾ÑÐ°Ð½Ð½Ð°Ñ Ð¼ÐµÑÐ¾Ð´Ð¸ÐºÐ° Ð¼Ð¾Ð¶ÐµÑ Ð¿ÑÐ¸Ð¼ÐµÐ½ÑÑÑÑÑ ÐºÐ°Ðº ÑÐºÑÐ¸Ð½Ð¸Ð½Ð³Ð¾Ð²Ð°Ñ. Ð¢Ð°Ðº ÐºÐ°Ðº Ð´Ð°Ð½Ð½Ð°Ñ ÑÐµÑÑ-ÑÐ¸ÑÑÐµÐ¼Ð° Ð² 100% ÑÐ»ÑÑÐ°ÐµÐ² Ð²ÑÑÐ²Ð»ÑÐµÑ ÑÑÐ¾Ð¼Ð¾ÑÐ¾Ð¼Ð½ÑÑ Ð½ÐµÑÑÐ°Ð±Ð¸Ð»ÑÐ½Ð¾ÑÑÑ Ð² HRD-Ð¿Ð¾Ð»Ð¾Ð¶Ð¸ÑÐµÐ»ÑÐ½ÑÑ Ð¾Ð¿ÑÑÐ¾Ð»ÑÑ, Ð° ÑÐ°ÐºÐ¶Ðµ ÑÐ¿Ð¾ÑÐ¾Ð±Ð½Ð° ÑÐ°Ð·Ð»Ð¸ÑÐ°ÑÑ ÑÑÐ°Ð±Ð¸Ð»ÑÐ½ÑÐ¹ Ð¸ Ð½ÐµÑÑÐ°Ð±Ð¸Ð»ÑÐ½ÑÐ¹ Ð³ÐµÐ½Ð¾Ð¼, ÑÐ¾ Ð¿ÑÐ¸ Ð¿ÑÐ¸Ð¼Ðµ-Ð½ÐµÐ½Ð¸Ð¸ ÐµÐµ Ð² ÑÑÑÐ¸Ð½Ð½Ð¾Ð¹ Ð´Ð¸Ð°Ð³Ð½Ð¾ÑÑÐ¸ÐºÐµ 23,4 % Ð²ÑÐµÑ ÑÐ»ÑÑÐ°ÐµÐ² Ð½Ðµ Ð½ÑÐ¶Ð´Ð°ÐµÑÑÑ Ð² Ð±Ð¾Ð»ÐµÐµ Ð³Ð»ÑÐ±Ð¾ÐºÐ¸Ñ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸ÑÑ Ð½Ð° Ð¿ÑÐ¸ÑÑÑÑÑÐ²Ð¸Ðµ HRD Ð¿ÑÐ¸ Ð¿Ð¾Ð¼Ð¾ÑÐ¸ Ð¼ÐµÑÐ¾Ð´Ð¾Ð² NGS Ð¸Ð»Ð¸ MLPA, ÑÐµÐ¼ ÑÐ°Ð¼ÑÐ¼ ÑÐºÐ¾Ð½Ð¾Ð¼Ñ Ð´ÑÐ°Ð³Ð¾ÑÐµÐ½Ð½Ð¾Ðµ Ð²ÑÐµÐ¼Ñ Ð¸ ÑÐµÑÑÑÑÑ.
description: This work is devoted to the development of a screening method capable of detecting homologous recombination repair deficiency (HRD). To date, there are extremely expensive, time-consuming and resource-intensive test systems based on NGS and MLPA methods to determine HRD status. Therefore, the aim of this work was to develop a technique capable of predicting the presence of HRD in a human tumour, based on digital drop PCR as a faster and more affordable method. To achieve the goal, HRD-positive profiles in patients with BRCA-associated ovarian cancer were analysed and loci with the most frequent copy number abnormalities were identified. Such "points" of interest were copy disorder at loci on chromosomes 8, 13, 17, 19 and 22, including C-MYC gene amplification. Based on these observations, a methodology was designed using the ddPCR method. In the course of the work there were also defined the criteria of correspondence between the genome instability detected by the developed ddPCR test and the HRD status in the tumor material. In the course of the work, it was shown that the developed method can be used as a screening one. As this test system detects in 100% of cases chromosomal instability in HRD-positive tumours and can also distinguish between stable and unstable genome, 23.4% of all cases do not require more extensive testing for HRD presence using NGS or MLPA methods, thus saving precious time and resources.