A novel germline mutation of the PALB2 gene in a young Yakut breast cancer woman

• Published in: Ecography
• Main Authors: P. A. Gervas, A. Yu. Molokov, A. A. Zarubin, A. A. Ivanova, D. G. Tikhonov, N. S. Kipriyanova, A. N. Egorov, L. D. Zhuikova, N. A. Shefer, E. B. Topolnitskiy, V. A. Belyavskaya, L. F. Pisareva, E. L. Choynzonov, N. V. Cherdyntseva, П. А. Гервас, А. Ю. Молоков, А. А. Зарубин, А. A. Иванова, Д. Г. Тихонов, Н. С. Киприянова, А. Н. Егоров, Л. Д. Жуйкова, Н. А. Шефер, Е. Б. Топольницкий, В. А. Белявская, Л. Ф. Писарева, Е. Л. Чойнзонов, Н. В. Чердынцева
• Other Authors: The study was funded by the Russian Science Foundation, project № 22-25-20032, The Core Facility «Medical genomics», Tomsk NRMC., Исследование выполнено при финансовой поддержке РНФ, проект № 22-25-20032, Оборудование ЦКП «Медицинская геномика» Томского НИМЦ.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences 2022
• Subjects: PALB2; breast cancer; Asian ancestry ethnic groups in Russia; Yakut; рак молочной железы; этносы России азиатского происхождения; якуты; Circumpolar Health
• Online Access: https://www.siboncoj.ru/jour/article/view/2235; https://doi.org/10.21294/1814-4861-2022-21-4-72-79

Background. Breast cancer (BC) is the most common female malignancy worldwide. Partner And Localizer of BRCA2 gene (PALB2) is directly involved in DNA damage response. Germline mutation in PALB2 has been identified in breast cancer and familial pancreatic cancer cases, accounting for approximately 1–2% and 3–4%, respectively. The goal of this report was to describe new PALB2 mutation in a young Yakut breast cancer patient with family history of cancer. Material and Methods. Genomic DNA were isolated from blood samples and used to prepare libraries using a capture-based target enrichment kit, Hereditary Cancer Solution™ (SOP HiA GE NETICS , Switzerland), covering 27 genes (ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53 and XRCC2). Paired-end sequencing (2 × 150 bp) was conducted using NextSeq 500 system (Illumina, USA ). Results. Here we describe a case of a never-before-reported mutation in the PALB2 gene that led to the early onset breast cancer. We report the case of a 39-year-old breast cancer Yakut woman with a family history of pancreatic cancer. Bioinformatics analysis of the NGS data revealed the presence of the new PALB2 gene germinal frameshift deletion (NM_024675:exon1:c.47delA:p.K16fs). In accordance with dbPubMed ClinVar, new mutation is located in codon of the PALB2 gene, where the likely pathogenic donor splice site mutation (NM_024675.3:c.48+1delG) associated with hereditary cancer-predisposing syndrome has been earlier described. Conclusion. We found a new never-before-reported mutation in PALB2 gene, which probably associated with early onset breast cancer in Yakut indigenous women with a family history of pancreatic cancer. Актуальность. Рак молочной железы занимает лидирующие позиции по уровню заболеваемости во всем мире. Ген онкосупрессор PALB2 наряду с такими генами, как BRCA1, BRCA2, вовлечен в процессы репарации поврежденной ДНК. Частота встречаемости ...