Mutation Profile of Normal and Tumor Cells in a Patient with Multiple Myeloma: A Case Report

AUTOIMMUNE THROMBOCYTOPENIA

AS Zhuk1, II Kostroma2, EI Stepchenkova3,4, DV Kachkin3, OB Belopolskaya5, IV Zotova3,4, AD Garifullin2, SV Voloshin2,6, SV Gritsaev2, AYu Aksenova3

1 ITMO National Research University, 49 lit. A Kronverkskii pr-t, Saint Petersburg, Russian Federation, 197101

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

3 Saint Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

4 NI Vavilov Institute of General Genetics, Saint Petersburg branch, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

5 Bio-Bank Resource Center, Saint Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

6 SM Kirov Military Medical Academy, 6 Akademika Lebedeva ul., Saint Petersburg, Russian Federation, 194044

For correspondence: Elena Igorevna Stepchenkova, PhD in Biology, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034; Tel.: +7(905)282-57-72; e-mail: stepchenkova@gmail.com

For citation: Zhuk AS, Kostroma II, Stepchenkova EI, et al. Molecular Profiling of Normal and Tumor Plasma Cells in a Patient with Newly Diagnosed Multiple Myeloma: A Case Report. Clinical oncohematology. 2023;16(3):337–49. (In Russ).

DOI: 10.21320/2500-2139-2023-16-3-337-349

ABSTRACT1 

1The editorial board of the “Clinical Oncohematology. Fundamental Studies and Clinical Practice” reserves the right to independently interpret the results of next-generation sequencing (NGS) in line with international recommendations (ACMG/AMP, doi: 10.1038/gym.2015.30) and national guidelines (https://mgs.med-gen.ru/) for clinical use. Despite considerable points of divergence with personal views of the authors, the editorial board of the journal finds it possible to publish the present paper.

This paper is a case report of a patient with newly diagnosed multiple myeloma (MM) who underwent exome sequencing of peripheral blood lymphocytes and CD138+ tumor plasma cells prior to therapy. This patient showed some inherited genetic variants which are associated with underlying risk for MM. This patient’s genotype was reported to have some variants in the DNA repair genes, including inherited mutations in the RFDW3 and TP53 genes. They are involved in the maintenance of genome stability and accumulation rate of somatic mutations, including structural rearrangements and chromosome aberrations. A large number of structural variations

and mutational signature ID6 in the tumor genetic material point to the disruption of DNA damage repair. The tumor cell exome analysis yielded a profile of somatic mutations, also the mutations in the genes previously associated with MM, as well as a functional significance of the detected abnormalities. Somatic mutations also included damaging mutations and highly significant mutations in the other tumor-associated genes, such as ASCC3, TET3, and CHD1, as well as in the antimicrobial peptide-coding genes CAMP and HTN3. With the exception of an extra copy of 1q arm in the tumor plasma cell genome, the patient showed no genetic risk factors associated with poor prognosis of the disease. Based on literature, inherited (ABCB1 mutations) and somatic (trisomy 3) variations detected in the patient’s genetic material can be characterized as positive prognostic factors in MM.

Keywords: multiple myeloma, next-generation sequencing, exome, inherited mutations, somatic mutations.

Received: August 12, 2022

Accepted: May 20, 2023

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Статистика Plumx английский

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