Figure 1. Molecular and genomic... | Rockefeller University Press

Figure 1.

$Molecular and genomic characterization identifies a RET rearrangement in a patient with a three-decade history of papillary thyroid cancer. (A) Timeline from diagnosis (1988) to relapse and treatment with a RET inhibitor. Treatment with radioactive iodine; imaging results are summarized. Clinical timeline between 1988 and 2013 is compressed for clarity. (B–G) Histopathology (B–D; scale bar = 100 μm) and FISH (E–G; scale bar = 20 μm) from biopsy specimens obtained at the time of diagnosis in 1988 (B and E), from a pulmonary metastasis in 2013 (C and F), and from a bone metastasis in 2014 (D and G). Chromosomal rearrangement involving the RET gene was confirmed by FISH; arrowheads indicate rearrangement (E–G). In E–G, representative images from three replicates are shown. (H) Circos plot diagramming the index patient’s intrachromosomal rearrangement involving RET and CCDC6 (blue, chr10) overlayed with RET rearrangements identified in the TCGA papillary thyroid cancer cohort (n = 22). (I) tSNE (t-distributed stochastic neighbor embedding) analysis of gene expression comparing papillary thyroid cancers (TCGA) to the index patient (WCM271). Thyroid differentiation score is indicated by color; RET rearrangement status is indicated by icon. (J) Serum thyroglobulin (Tg, red) and CCDC6-RET allele fraction (blue) determined from circulating tumor cells are plotted over the indicated time; treatment with cabozantinib is indicated.$

Molecular and genomic characterization identifies a RET rearrangement in a patient with a three-decade history of papillary thyroid cancer. (A) Timeline from diagnosis (1988) to relapse and treatment with a RET inhibitor. Treatment with radioactive iodine; imaging results are summarized. Clinical timeline between 1988 and 2013 is compressed for clarity. (B–G) Histopathology (B–D; scale bar = 100 μm) and FISH (E–G; scale bar = 20 μm) from biopsy specimens obtained at the time of diagnosis in 1988 (B and E), from a pulmonary metastasis in 2013 (C and F), and from a bone metastasis in 2014 (D and G). Chromosomal rearrangement involving the RET gene was confirmed by FISH; arrowheads indicate rearrangement (E–G). In E–G, representative images from three replicates are shown. (H) Circos plot diagramming the index patient’s intrachromosomal rearrangement involving RET and CCDC6 (blue, chr10) overlayed with RET rearrangements identified in the TCGA papillary thyroid cancer cohort (n = 22). (I) tSNE (t-distributed stochastic neighbor embedding) analysis of gene expression comparing papillary thyroid cancers (TCGA) to the index patient (WCM271). Thyroid differentiation score is indicated by color; RET rearrangement status is indicated by icon. (J) Serum thyroglobulin (Tg, red) and CCDC6-RET allele fraction (blue) determined from circulating tumor cells are plotted over the indicated time; treatment with cabozantinib is indicated.

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