Supplementary Figures S1-S10 from Comprehensive Genetic Characterization of Human Thyroid Cancer Cell Lines: A Validated Panel for Preclinical Studies
Authors: Landa Iñigo , Pozdeyev Nikita , Korch Christopher , Marlow Laura A. , Smallridge Robert C. , Copland John A. , Henderson Ying C. , Lai Stephen Y. , Clayman Gary L. , Onoda Naoyoshi , Tan Aik Choon , Garcia-Rendueles Maria E.R. , Knauf Jeffrey A. , Haugen Bryan R. , Fagin James A. , Schweppe Rebecca E. 
Published: April 2023

<p>Supplementary Figure S1. Copy number alteration profile for TERT locus in cell lines harboring homozygous TERT promoter mutations. Copy number changes are expressed as shades of red (gain) or blue (loss). Names of cell lines and log-ratio (lr) values are shown. Supplementary Figure S2. Genome-wide copy number alteration profile of PTC-derived cell lines (top) vs. ATC-derived cell lines (bottom). Chromosome numbers are shown on the top panel. Copy number changes are expressed as shades of red (gain) or blue (loss). Supplementary Figure S3. Representation of the chromosomal location for the 16 recurrent copy number alterations identified by GISTIC in 58 thyroid cancer cell lines. Supplementary Figure S4. Hierarchical clustering of gene expression profiles of thyroid cancer cell lines. Spearman correlation distance metric and Ward agglomeration method were used. Colors identify cell lines originating from tumors of different histologic subtypes. Font color indicates the histological type of the primary tumor from which these cell lines were generated, as follows: red= anaplastic; purple= poorly differentiated; green=follicular; blue= papillary thyroid cancer. Colored dots represent driver alteration: blue= BRAFV600E; orange= N-/H-/KRAS; purple= CCDC6-RET; green= NF1; yellow= MKRN1-BRAF; gray= FGFR2-OGDH; black= unknown. Supplementary Figure S5. Expression of individual genes in the thyroid differentiation signature. Supplementary Figure S6. Correlation of BRS calculated using our algorithm vs. the algorithm published by TCGA. The color of the circles indicates tumor genotype: blue- BRAFV600E, red- RAS gene mutation, green - neither BRAFV600E nor RAS mutation, orange - both BRAFV600E and RAS gene mutations present. Tumors with low BRS are BRAFV600E-like; tumors with high BRS are RAS-like. Supplementary Figure S7. Representative pictures of BAM files from MSK-IMPACT sequencing of CUTC5 specimens for three mutations: A. BRAF p.V600E; B. TP53 C135W; and C. ARID1A E1108*. Each panel shows the sequencing reads for the cell line (top) and primary tumor (bottom). The reference allele and protein translation is shown in the bottommost area, whereas the alternative allele is highlighted in the sequencing reads within each panel. Percentages on the left represent the frequency of the alternative allele in each of the samples tested. All three mutations are detected at low frequencies in the original pleural effusion sample, from which CUTC5 cell line was established. Supplementary Figure S8. Evolution of allelic frequencies from thyroid primary tumors to cell lines for A. TERT promoter; and B. TP53. Graphic representation of the alternative allele frequencies ("Alt Allele Freq"). Cell line names are color-coded on the right side of each graph. All TERT promoter mutations are the canonical c.-124C>T or c.-146C>T, whereas TP53 mutations are indicated. Supplementary Figure S9. Genome-wide copy number alteration profile of primary tumor/cell line and/or patient-derived xenograft (PDX) paired samples from 11 patients. Chromosome numbers are shown on the top panel. Copy number changes are expressed as shades of red (gain) or blue (loss). Colored dots indicate specimen types: cell line (green), primary tumor (orange) or PDX (purple). Cell line names are provided. Supplementary Figure S10. Global MSK-IMPACT copy number profile of THJ560 paired samples. Sample-centered representation of the copy number alterations, expressed as log2 ratios, for primary tumor (top panel), cell line (middle panel) and patient-derived xenograft (bottom panel). Table inserts show the top deletions, corresponding to the CDKN2A/CDKN2B locus for the cell line and xenograft, which are absent in the primary tumor.</p>