Faculty Bibliography

Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.

Metaplastic breast cancer (MPBC) is a rare subtype that accounts for <1% of all breast cancers. Although these are typically "triple negative," they are relatively chemotherapy-refractory compared to conventional triple negative invasive breast cancers with more aggressive features and an overall poor prognosis. MPBC is a heterogeneous group of tumors that are enriched for TP53 and PIK3CA mutations, and have been found to have high PD-L1 expression though the mechanisms underlying its immunogenicity remain unclear. We perform comprehensive genomic profiling in the largest MPBC dataset (n = 192) to date and assess for other potential biomarkers of immune response.

Purpose/UNASSIGNED:alterations in lung cancer. Patients and Methods/UNASSIGNED:base substitutions, short insertions and deletions, copy number changes, and rearrangements. Results/UNASSIGNED:V600E inhibition are demonstrated. Conclusion/UNASSIGNED:alterations represent a subgroup of lung cancers in which targeted therapy should be considered.

INTRODUCTION:) have previously been identified in lung adenocarcinomas, but their frequency and clinical significance is unknown. METHODS:We prospectively analyzed 8551 consecutive lung adenocarcinomas using hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians for the purpose of making therapy decisions. RESULTS:mutations. HER2 TMD mutations (V659 and G660) are found in other non-NSCLC malignancies, and analogous TMD mutations are also found in EGFR, HER3, and HER4. CONCLUSION:HER2 TMD mutations represent rare but distinct targetable driver mutations in lung adenocarcinoma. CGP capable of detecting diverse HER2 alterations, including HER2 TMD mutations, should be broadly adopted to identify all patients who may benefit from HER2-targeted therapies.

Purpose To identify the ability of computer-derived three-dimensional (3D) computed tomographic (CT) segmentation techniques to help differentiate lung adenocarcinoma subtypes. Materials and Methods This study had institutional research board approval and was HIPAA compliant. Pathologically classified resected lung adenocarcinomas (n = 23) with thin-section CT data were identified. Two readers independently placed over-inclusive volumes around nodules from which automated computer measurements were generated: mass (total mass) and volume (total volume) of the nodule and of any solid portion, in addition to the solid percentage of the nodule volume (percentage solid volume) or mass (percentage solid mass). Interobserver agreement and differences in measurements among pathologic entities were evaluated by using t tests. A multinomial logistic regression model was used to differentiate the probability of three diagnoses: invasive non-lepidic-predominant adenocarcinoma (INV), lepidic-predominant adenocarcinoma (LPA), and adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA). Results Mean percentage solid volume of INV was 35.4% (95% confidence interval [CI]: 26.2%, 44.5%)-higher than the 14.5% (95% CI: 10.3%, 18.7%) for LPA (P = .002). Mean percentage solid volume of AIS/MIA was 8.2% (95% CI: 2.7%, 13.7%) and had a trend toward being lower than that for LPA (P = .051). Accuracy of the model based on total volume and percentage solid volume was 73.2%; accuracy of the model based on total mass and percentage solid mass was 75.6%. Conclusion Computer-assisted 3D measurement of nodules at CT had good reproducibility and helped differentiate among subtypes of lung adenocarcinoma. (c) RSNA, 2016.

A 29-year-old man presented with a 5-month history of worsening dry cough, exertional dyspnea, chest tightness, and palpitations. He had been treated by his primary care physician with trials of guaifenesin/codeine, azithromycin, albuterol, and omeprazole without improvement. He denied wheezing, fever, sweats, anorexia, joint pain, swelling, or rash. He had no past medical history. He denied a history of tobacco smoking or IV drug use. He kept no pets, worked as a manager in an office environment, and had no history of occupational inhalational exposure. He reported using aerosolized insect spray to eradicate bed bugs in his house shortly before the cough began but did not report any acute symptoms when using the spray.