TY - JOUR

T1 - Мутационный профиль генома нормальных и опухолевых клеток у больного множественной миеломой (клинический случай)

AU - Жук, Анна Сергеевна

AU - Кострома, Иван Иванович

AU - Степченкова, Елена Игоревна

AU - Качкин, Даниил Валерьевич

AU - Белопольская, Олеся Борисовна

AU - Зотова, Ирина Владимировна

AU - Гарифуллин, Андрей

AU - Волошин, Сергей Владимирович

AU - Грицаев, Сергей Васильевич

AU - Аксенова, Анна Юрьевна

PY - 2023/3/3

Y1 - 2023/3/3

N2 - 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 protein 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.

AB - 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 protein 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.

KW - exome

KW - inherited mutations

KW - multiple myeloma

KW - next-generation sequencing

KW - somatic mutations

UR - https://www.mendeley.com/catalogue/8c50409a-3436-3e24-859b-26f4295179ed/

U2 - 10.21320/2500-2139-2023-16-3-337-349

DO - 10.21320/2500-2139-2023-16-3-337-349

M3 - статья

VL - 16

SP - 337

EP - 349

JO - Klinicheskaya Onkogematologiya/Clinical Oncohematology

JF - Klinicheskaya Onkogematologiya/Clinical Oncohematology

SN - 1997-6933

IS - 3

ER -