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Co-authored-by: Stephanie <[email protected]>

content/03.results.md

@@ -200,15 +200,14 @@ Tumor types with the highest median _TP53_ scores were those known to harbor som
 
 To further validate the classifier's accuracy, we assessed _TP53_ scores for patients with LFS, hypothesizing that all of these tumors would have high scores.
 Indeed, we observed higher scores in 8/10 tumors from LFS patients (**Table S3**).
-Although we observed low _TP53_ scores in two tumors from LFS patients (BS_DEHJF4C7 with a score of 0.09 and BS_ZD5HN296 with a score of 0.28), we confirmed from pathology reports that both patients were diagnosed with LFS and had a pathogenic germline variant in _TP53_.
-In addition, the tumor purity of these two LFS tumors was low (16% and 37%, respectively), suggesting the classifier may require a certain level of tumor purity to achieve good performance, as we expect _TP53_ to be intact in normal cells.
-We posit that these transcriptomic scores can be utilized to infer _TP53_ function in the absence of a predicted oncogenic _TP53_ alteration or DNA sequencing in general.
+Although two tumors from LFS patients had low _TP53_ scores (`BS_DEHJF4C7` at 0.09 and `BS_ZD5HN296` at 0.28), we confirmed from pathology reports that both patients were diagnosed with LFS and had a pathogenic germline variant in _TP53_.
+These two LFS tumors also had low tumor purity (16% and 37%, respectively), suggesting the classifier may require a certain level of tumor content for accurate performance, as _TP53_ should be intact in normal cells.
+These transcriptomic scores could be utilized to infer _TP53_ function in the absence of a predicted oncogenic _TP53_ alteration or DNA sequencing in general.
 
 We used gene expression data to predict telomerase activity using EXpression-based Telomerase ENzymatic activity Detection (`EXTEND`) [@doi:10.1038/s41467-020-20474-9] as a surrogate measure of malignant potential [@doi:10.1038/s41467-020-20474-9; @doi:10.1093/carcin/bgp268], such that higher `EXTEND` scores indicate higher telomerase activity.
-While we did not find that tumors with _TERT_ promoter (TERTp) mutations (N = 6) had significantly higher telomerase activity scores than non-mutated tumors (Wilcoxon p-value = 0.1196), we observed that `EXTEND` scores significantly correlated with _TERC_ (R = 0.619, p < 0.01) and _TERT_ (R = 0.491, p < 0.01) expression (**Figure {@fig:S5}B-C**).
+While `EXTEND` scores were not significantly higher in tumors with _TERT_ promoter (TERTp) mutations (N = 6; Wilcoxon p-value = 0.1196), scores were significantly correlated with _TERC_ (R = 0.619, p < 0.01) and _TERT_ (R = 0.491, p < 0.01) log2 FPKM expression values (**Figure {@fig:S5}B-C**).
 Since catalytically-active telomerase requires a combination of full-length _TERT_, _TERC_, as well as accessory proteins [@url:https://pubmed.ncbi.nlm.nih.gov/9751630], we expect that `EXTEND` scores may not be exclusively correlated with _TERT_ alterations and expression.
-Next, we found aggressive tumors such as HGGs (DMGs and other HGGs) and MB had high `EXTEND` scores (**Figure {@fig:Fig4}D**), while low-grade lesions such as schwannomas, GNGs, DNETs, and other LGGs had among the lowest scores (**Table S3**).
-These findings support previous reports of a more aggressive phenotype in tumors with higher telomerase activity [@doi:10.1007/s13277-016-5045-7; @doi:10.1038/labinvest.3700710; @doi:10.1007/s12032-016-0736-x; @doi:10.1111/j.1750-3639.2010.00372.x].
+While aggressive tumors such as DMGs, other HGGs, and MB had high `EXTEND` scores (**Figure {@fig:Fig4}D**), low-grade lesions such as schwannomas, GNGs, DNETs, and other LGGs had among the lowest scores (**Table S3**), supporting previous reports that more aggressive tumor phenotypes have higher telomerase activity [@doi:10.1007/s13277-016-5045-7; @doi:10.1038/labinvest.3700710; @doi:10.1007/s12032-016-0736-x; @doi:10.1111/j.1750-3639.2010.00372.x].
 
 #### Hypermutant tumors share mutational signatures and have dysregulated **_TP53_**