Cartilage can be shaped by scoring. In an exploratory study in living adult animals, this phenomenon was demonstrated in cartilage of the nasal septum. Bending was observed immediately after superficial scoring of the cartilage surface, and the cartilage always warped in the direction away from the scored side. The scored piece of cartilage still showed its initially distorted shape 10 weeks after primary surgery. In ex vivo experiments, a clear relation between incision depth and bending of septal cartilage was observed. Under these controlled conditions, the variation between different septa was small. Deformation of the septal specimens was increased by introducing single superficial incisions deepening to half the thickness of the cartilage. A positive correlation between incision depth and bending was demonstrated. A model was used to accurately predict the degree of bending of the cartilage after making an incision of a particular depth. Hence, the effect of cartilage scoring can be predicted. Because the results of this controlled study showed excellent reproducibility for different septa, it is expected that this model can be extrapolated to human nasal septum cartilage. This would enable the surgeon to better predict the result of cartilage scoring, either preoperatively or perioperatively.

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The incidence and mortality of early-onset colorectal cancer (EOCRC) are rising; outcomes appear to differ by race and ethnicity. We aimed to assess differences in mutational landscape and gene expression of EOCRC by racial and ethnic groups (Non-Hispanic Asian, Non-Hispanic Black, Non-Hispanic White, White Hispanic) using data from AACR Project GENIE (10.2) and University of Texas Southwestern, the latter enriched in Hispanic patients. All statistical tests were 2-sided. Of 1,752 EOCRC patients, Non-Hispanic Black patients had higher rates of KRAS mutations (60.9%, p = .001, q = 0.015) and Non-Hispanic White and Non-Hispanic Black patients had higher rates of APC mutations (77.1% and 76.6% among Non-Hispanic White and Non-Hispanic Black patients, respectively; p = .001, q = 0.015) via the Fisher exact test with Benjamini-Hochberg correction. Using R packages DESeq2 and clusterProfiler, we found that White Hispanic patients had increased expression of genes involved in oxidative phosphorylation (p < .001, q = 0.025). Genomic profiling has the potential to identify novel diagnostics and influence individualized treatment options to address the currently limited prognosis of EOCRC.

Purpose: Prior research in the molecular correlates of disparities in incidence and outcomes of colorectal cancer (CRC) by race and ethnicity have typically used self-reported or observed categories, which can be missing or inaccurate. Furthermore, race and ethnicity do not always capture genetic similarity well, particularly in admixed populations. To overcome these limitations, we examined associations of CRC tumor molecular profiles with genetic ancestry. Experimental Design: Sequencing was performed with the Tempus xT NGS 648-gene panel and whole exome capture RNA-Seq for 8,454 CRC patients. Genetic ancestry proportions were estimated for five continental groups, Africa (AFR), Americas (AMR), East Asia (EAS), Europe (EUR), and South Asia (SAS), using ancestry informative markers. We assessed association of genetic ancestry proportions and genetic ancestry-imputed race and ethnicity categories with somatic mutations in relevant CRC genes and in expression profiles, including consensus molecular subtypes (CMS). Results: Increased AFR ancestry was associated with higher odds of somatic mutations in APC, KRAS and PIK3CA and lower odds of BRAF mutations. Additionally, increased EAS ancestry was associated with lower odds of mutations in KRAS, EUR with higher odds in BRAF, and the Hispanic/Latino category with lower odds in BRAF. Greater AFR ancestry and the non-Hispanic Black category were associated with higher than expected CMS3, while patients in the Hispanic/Latino category had higher indeterminate CMS. Conclusions: Use of genetic ancestry enables identification of molecular differences in CRC tumor mutation frequencies and gene expression that may underlie observed differences by race and ethnicity, and suggests that subtype classifications such as CMS may benefit from more diversity in representation.