Derivation of doxorubicin mutational signatures in cancer.

Two experimentally derived doxorubicin mutational signatures, SBS-doxorubicin-1 (C > A) and SBS-doxorubicin-2 (T > C), are detected in 83% of doxorubicin-treated patient samples.

• Why it matters: The work addresses whether doxorubicin exposure leaves a nonrandom, genome-wide somatic mutation pattern that can be recognized in real patient tumors.
• What they did: Cells were exposed to doxorubicin via continuous constant-dose single-cell clone sequencing and pulsed escalating-dose bulk sequencing, then signatures were searched in 10 bulk immune-sorted samples from three follicular lymphoma/diffuse large B cell lymphoma patients plus two metastatic samples from one renal medullary carcinoma patient.
• The result: Both signatures were found in 83% of those samples, with the remaining samples containing either SBS-doxorubicin-1 or SBS-doxorubicin-2, enabling signature-based detection of doxorubicin exposure in these cohorts.

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