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Fig. 5 | Genome Medicine

Fig. 5

From: Cell-free DNA analysis reveals POLR1D-mediated resistance to bevacizumab in colorectal cancer

Fig. 5

Alternating POLR1D and ERBB2 amplifications in serial plasma analyses of patient C129. a Genome-wide log2 ratio plots of plasma samples from C129 obtained before treatment with cetuximab (first), 160 days (second) after cetuximab, before bevacizumab (third), and 138 days (fourth) after bevacizumab. The insets illustrate the respective tumor fraction (TF) for each analysis and enlarged log2 ratio plots of chromosome 13 and 17, the first and the last sample showing gain of chromosome 13, with the highest copy number on chr13q12.2, the region harboring POLR1D. The middle 2 samples show a gain of chromosome 17 with the highest copy number on chr17q12, harboring ERBB2. The copy number color code is as in Fig. 4. b Plot illustrating blood collection time points. Red line: POLR1D copy number changes measured by dPCR. A decrease in POLR1D copy number was detected until day 274 during cetuximab treatment. After switching to bevacizumab, POLR1D copy number increased back within 138 days. Green line: ERBB2 copy number changes (dPCR). ERBB2 copy number increased until day 274 (during cetuximab treatment). After switching to bevacizumab, ERBB2 copy number decreased back within 138 days. Blue line: CEA levels decreased in the first 3 samples and slightly increased in the fourth sample. After a slight decrease in the fifth sample, CEA continuously increased up until the last sample. Black line: CA 19-9 remained at low levels across all samples. Gray bar: tumor fraction estimated with ichorCNA. c Four CT images obtained on day 6 and day 212 of cetuximab treatment, before bevacizumab treatment (day 268), and 160 days after bevacizumab treatment (day 434). No significant changes were identified on day 212, consistent with stable disease. On day 268, the pre-present lung metastasis lesion became larger in the right lung and pleural effusion appeared in the left lung, indicating progressive disease. On day 434, this pre-present lesion became larger and new metastasis lesions appeared. Pleural effusion increased, and progressive disease was designated

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