Accelerated single cell seeding in relapsed multiple myeloma.

Nature Communications
Heather J LandauFrancesco Maura

Abstract

Multiple myeloma (MM) progression is characterized by the seeding of cancer cells in different anatomic sites. To characterize this evolutionary process, we interrogated, by whole genome sequencing, 25 samples collected at autopsy from 4 patients with relapsed MM and an additional set of 125 whole exomes collected from 51 patients. Mutational signatures analysis showed how cytotoxic agents introduce hundreds of unique mutations in each surviving cancer cell, detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature. Thus, a unique, single-cell genomic barcode can link chemotherapy exposure to a discrete time window in a patient's life. We leveraged this concept to show that MM systemic seeding is accelerated at relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high-dose melphalan therapy and autologous stem cell transplant.

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Citations

Aug 8, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francesco MauraGareth J Morgan
Jan 5, 2021·Blood Cancer Discovery·Even H RustadFrancesco Maura
Jan 24, 2021·Leukemia·Benjamin DiamondFrancesco Maura
Jan 29, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francesco MauraOla Landgren
May 8, 2021·Seminars in Cell & Developmental Biology·Francesco MauraGareth J Morgan
May 21, 2021·Leukemia·Francesco MauraOla Landgren
Aug 12, 2021·Nature Communications·Oriol PichNuria Lopez-Bigas
Aug 29, 2021·Nature Communications·Kylee H MaclachlanFrancesco Maura

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Methods Mentioned

BETA
biopsies
PCR

Software Mentioned

Isabl
BWA
Pindel
BRASS
MEM
mmsig
SigProfiler
CaVEMan

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