Figure 4.

Monitoring multiple tumor-specific chromosomal rearrangements in circulating DNA

• A–C Plasma levels of circulating tumor DNA (ctDNA), quantified using ddPCR, for three patients with known eventual recurrence. Specific rearrangements are indicated by colored markers and labeled according to cytogenetic nomenclature (t denotes translocation, inv is inversion, and del is deletion). The recurrence by ctDNA time-point is defined as the earliest follow-up plasma sample (after surgery) with ctDNA detected at a level greater than 0% (compared to total cell-free circulating DNA) for at least one rearrangement. All relevant clinical events are indicated above by arrows, time gain by ctDNA-based detection is indicated by a green horizontal bar, and radiation (RT), endocrine, and cytotoxic treatments are indicated by colored shading. T = tamoxifen; FEC = fluorouracil, epirubicin, and cyclophosphamide. See Supplementary Fig S2 for ctDNA time-course plots with clinical annotations for all patients.
• D Correlative magnetic resonance (MR; T1 weighted) and computed tomography (CT) imaging for patient EM11 corresponding to the red arrows in (B). In the MR, low T1 signal (dark) is present in the entire second thoracic vertebra and as punctate lesions in several vertebrae in the middle thoracic spine. The CT 15 months later shows sclerosis (white) in multiple additional thoracic vertebrae, consistent with progression of metastatic disease.
• E, F ctDNA plots for two patients with long-term disease-free survival.