Cover ImageThe incidence of early-onset colorectal cancer (CRC) is steadily increasing, but the molecular features and underlying disparities that surround this disease have not been fully explored. To examine early-onset colorectal tumor biology across diverse populations, Holowatyj and colleagues analyzed 6,903 non-Hispanic white (NHW), non-Hispanic Black (NHB), or Asian or Pacific Islander (API) patients with colorectal adenocarcinoma (including 2,016 patients with early-onset CRC) together with clinical-grade targeted sequencing and clinicodemographic information from AACR Project GENIE. Among patients with early-onset hypermutated CRC, higher adjusted tumor mutation rates were observed in NHB patients but not API patients compared with NHW patients. Significant differences in mutation frequencies between racial/ethnic groups were observed in LRP1B, FLT4, FBXW7, RNF43, ATRX, APC, and PIK3CA, with APC, FLT4, and FAT1 showing differences between early-onset and late-onset nonhypermutated CRC. Moreover, sex-specific alterations to mutation frequencies occurred in EP300, BRAF, WRN, KRAS, AXIN2, and SMAD2. Together, these results define racial/ethnic and sex-specific genomic patterns in early-onset nonhypermutated CRC as well as provide initial clues into genomic features underlying disparities of this increasingly prevalent disease. For more information, see the article by Holowatyj and colleagues on page 570.Close Modal
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Racial/Ethnic and Sex Differences in Somatic Cancer Gene Mutations among Patients with Early-Onset Colorectal Cancer
This consortium study defined distinct somatic cancer gene mutation patterns by race/ethnicity and sex among patients with early-onset colorectal cancer (CRC), yielding novel biological clues into early-onset CRC disparities.
CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
CD19/CD20 bispecific CAR-T cells enriched in naive and memory phenotypes achieve robust antitumor efficacy and durability of response with minimal toxicity in patients with relapsed and refractory non-Hodgkin lymphoma.
NVL-520 Is a Selective, TRK-Sparing, and Brain-Penetrant Inhibitor of ROS1 Fusions and Secondary Resistance Mutations
NVL-520, a selective macrocyclic inhibitor of ROS1, demonstrated antitumor activity in patient case studies of ROS1 inhibitor–refractory lung cancers without observed neurologic toxicities attributed to TRK inhibition.
Detecting Liver Cancer Using Cell-Free DNA Fragmentomes
A machine learning model using multifeature fragmentome data from genome-wide cell-free DNA analyses detected hepatocellular carcinoma with high sensitivity and specificity in average and high-risk populations, including in early-stage disease.
Nucleosome Patterns in Circulating Tumor DNA Reveal Transcriptional Regulation of Advanced Prostate Cancer Phenotypes
New methods for the analysis of circulating tumor DNA from patient-derived xenograft plasma inform on tumor gene regulation and provide a blood-based signature for classifying prostate cancer phenotypes in clinical patient samples.
Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA
Multiomic profiling of malignant peripheral nerve sheath tumors reveals genomic events that underlie tumor evolution including extensive somatic copy-number alterations (SCNA), with detection of specific SCNAs in cell-free DNA being able to predict prognosis.
Discovery of Targets for Immune–Metabolic Antitumor Drugs Identifies Estrogen-Related Receptor Alpha
The computational tool BipotentR was used to reveal drug targets that can inhibit tumor growth by concurrent immune activation and inhibition of a separate oncogenic pathway, leading to identification of ESRRA as a top immune–metabolic target.
LZTR1 Mutation Mediates Oncogenesis through Stabilization of EGFR and AXL
LZTR1 mutations stabilize and activate EGFR and AXL proteins in cancer, thus conferring specific vulnerability of LZTR1-mutant cancers to combination treatment with EGFR and AXL inhibitors.
Mutant NPM1 Hijacks Transcriptional Hubs to Maintain Pathogenic Gene Programs in Acute Myeloid Leukemia
Mutant NPM1 in leukemia obtains neomorphic activity to hijack active HOXA/B and MEIS1 transcription on chromatin via the association of XPO1 and blocks the histone deacetylase activity associated with myeloid differentiation.
Mutant NPM1 Directly Regulates Oncogenic Transcription in Acute Myeloid Leukemia
NPM1c is recruited to self-renewal–associated genes and enhances their transcription in cooperation with the MLL histone methyltransferase complex, which can be targeted by Menin–MLL inhibitors.
A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas
The survival of a subset of carcinoma cells is dependent on the function of the BIRC6 ubiquitin ligase complex, which prevents aberrant activation of the integrated stress response via degradation of the HRI kinase.
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