5'UTR gene regions in germline DNA sequencing panels: lessons from the analysis of breast and ovarian cancer patients of Tatar and Bashkir ethnic origin.
Anna P Sokolenko, Aigul R Venina, Alexandr A Romanko, Evgenia V Belogubova, Alexandr V Sultanbayev, Vadim E Askarov, Gulnara K Mukhamediarova, Elvina Kh Bakaeva, Maria V Syomina, Tatiana Yu Velyukhova, Elena V Preobrazhenskaya, Alexandr V Togo, Evgeny N Imyanitov
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Abstract
Background: Tatars and Bashkirs are large and closely related ethnic communities that reside in the territory of the Russian Federation but have managed to preserve their national identity through the course of history.
Methods: This study included 446 Tatars, 53 Bashkirs, and 26 women of mixed Tatar-Bashkir ethnicity. Germline DNA analysis was performed for 349 breast cancer (BC) patients with clinical features of hereditary disease (family history, or young onset (
Results: BRCA1 pathogenic variants (PVs) were detected in 63 women; surprisingly, five Slavic founder alleles accounted for 30 (48%) of the BRCA1 PVs. The genuine Tatar BRCA1 allele, c.5161C > T, was observed in 11 subjects. Among 27 women with BRCA2 PVs, six and five women were carriers of the c.-39-1_-39del and c.468dup variants, respectively. The loss-of-heterozygosity (LOH) test confirmed the pathogenic nature of the c.-39-1_-39del [rs758732038] allele, which is located in the 5'UTR of BRCA2. Analysis of other BC-associated genes revealed single instances of PVs affecting PALB2, TP53, ATM, RAD51, and RAD51D genes.
Conclusion: Tatars and Bashkirs, which are ethnically and religiously separated from Russians, carry an unexpectedly high proportion of Slavic BRCA1/2 founder alleles. The identification of recurrent Tatar/Bashkir BRCA2 pathogenic 5'UTR variant c.-39-1_-39del calls for a systematic analysis of regulatory regions of cancer-predisposing genes in patients with missing heritability.
期刊介绍：
In recent years clinical cancer genetics has become increasingly important. Several events, in particular the developments in DNA-based technology, have contributed to this evolution. Clinical cancer genetics has now matured to a medical discipline which is truly multidisciplinary in which clinical and molecular geneticists work together with clinical and medical oncologists as well as with psycho-social workers.
Due to the multidisciplinary nature of clinical cancer genetics most papers are currently being published in a wide variety of journals on epidemiology, oncology and genetics. Familial Cancer provides a forum bringing these topics together focusing on the interests and needs of the clinician.
The journal mainly concentrates on clinical cancer genetics. Most major areas in the field shall be included, such as epidemiology of familial cancer, molecular analysis and diagnosis, clinical expression, treatment and prevention, counselling and the health economics of familial cancer.
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