RT Journal Article SR Electronic T1 Distinctive desmoplastic 3D morphology associated with BRAFV600E in papillary thyroid cancers JF bioRxiv FD Cold Spring Harbor Laboratory SP 160127 DO 10.1101/160127 A1 M. Tarabichi A1 A. Antoniou A1 S. Le Pennec A1 D. Gacquer A1 N. de Saint Aubain A1 L. Craciun A1 T. Cielen A1 I. Laios A1 D. Larsimont A1 G. Andry A1 J.E. Dumont A1 C. Maenhaut A1 V. Detours YR 2017 UL http://biorxiv.org/content/early/2017/07/06/160127.abstract AB Textbooks suggest that cancers are compact balls with an inner core and an invasive front in contact with non-cancerous cells, and that tumor growth is driven by tumor cell proliferation subsequent to oncogenic genome mutations. We reconstructed at histological scale the 3D volume occupied by tumor cells in two regions of a BRAFV600E-mutated papillary thyroid carcinoma (PTC) with low tumor purity, as determined by sequencing, but initially considered high purity during pathology review. In contrast with a compact ball, tumor cells formed a sparse mesh deeply embedded within the stroma. The concepts of inner core and invasive front broke down in this morphology: all tumor cells were within short distance from the stroma. The fibrous stroma was highly cellular and proliferative, a result confirmed in an independent series. This case was not unique: 3.5% of The Cancer Genome Atlas PTCs had purities <25%, 27% were below the 60% purity inclusion criterion. Moreover, the presence of BRAFV600E was associated with extensive fibrosis, high stromal activation, and dedifferentiation. Thus, non-tumor cells make most of the tumor mass and contribute to its expansion in a significant fraction of BRAFV600E PTCs. Therapeutics targeting the tumor-stroma crosstalk could be beneficial in this context.