Mutational landscape of triple-negative breast cancer in African American women.

African American (AA) women have the highest incidence of triple-negative breast cancer (TNBC) among all racial groups, but are underrepresented in cancer genomic studies. In 462 AA women with TNBC, we characterized the tumor mutational landscape by whole-exome sequencing and RNA sequencing. We unveiled a high-resolution mutational portrait of TNBC in AA women reminiscent of that in Asian and non-Hispanic white women, with no evidence of associations of mutational features with African ancestry.

Training the Next Generation of Researchers to Advance Cancer Health Equity: Five Years of Experience from the Florida-California Cancer Research, Education and Engagement (CaRE) Health Equity Center.

The underrepresentation of racial and ethnic minority scientists in research is a significant barrier to eliminating cancer health disparities. There is a compelling need to develop a cadre of racially and ethnically diverse, well-trained scientists to effectively meet the nation's biomedical, behavioral, population, and clinical cancer research needs. The Florida-California Cancer Research, Education and Engagement Health Equity Center's program focuses on training this underrepresented workforce.

Optimizing participant and community engagement in cancer genomic sequencing research.

Purpose: We describe strategies implemented across research centers of the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network to optimize engagement of participants and communities in cancer genomics research. We also present consensus definitions of engagement and engagement optimization, informed by our shared experiences in the Network.

Methods: Key informant interviews and a document review identified engagement and optimization strategies across PE-CGS research centers.

Resolving spatial subclonal genomic heterogeneity of loss of heterozygosity and extrachromosomal DNA in gliomas.

Mapping the spatial organization of DNA-level somatic copy number changes in tumors can provide insight to understanding higher-level molecular and cellular processes that drive pathogenesis. We describe an integrated framework of spatial transcriptomics, tumor/normal DNA sequencing, and bulk RNA sequencing to identify shared and distinct characteristics of an initial cohort of eleven gliomas of varied pathology and a replication cohort of six high-grade glioblastomas. We identify focally amplified extrachromosomal DNA (ecDNA) in four of the eleven initial gliomas, with subclonal tumor heterogeneity in two EGFR-amplified grade IV glioblastomas.

Whole-Exome Sequencing of Total Joint Arthroplasty Patients Who Have Known Pulmonary Embolism: A Pilot Study.

Background: The purpose of this study was to identify genetic mutations in exome sequences of patients who had a history of pulmonary embolism (PE) after total joint arthroplasty (TJA).

Methods: From June 2017 to August 2021, 21 patients who had a history of TJA and subsequent postoperative PE were enrolled in three academic institutions for whole-exome sequencing. Their average age was 64 years (range, 46 to 81), and 15 (71.

Epigenetic Modulation, Intra-tumoral Microbiome and Immunity in Early Onset Colorectal Cancer.

The incidence of colorectal cancer (CRC) in young adults (age of diagnosis < 50 years old) has been rapidly increasing. Although ~20% of early-onset (EO) CRC cases are due to germline mutations, the etiology of the majority of EOCRC cases remains poorly understood. Non-genetic factors such as environmental exposure and lifestyle changes are likely to have a direct link to the increased incidence of sporadic EOCRC.

Somatic Genomic Profiling of Pancreatic Ductal Adenocarcinomas From a Diverse Cohort of Patients.

Objectives: Black/African American (B/AA) pancreatic ductal adenocarcinoma (PDAC) patients have worse clinical outcomes than White patients and are underrepresented in genomic databases. We aimed to expand our understanding of the PDAC somatic landscape from a diverse cohort.

Materials And Methods: Formalin-fixed paraffin-embedded specimens from 24 surgically resected PDAC cases were collected, with self-reported race/ethnicity.

Association of ESR1 Germline Variants with TP53 Somatic Variants in Breast Tumors in a Genome-wide Study.

Unlabelled: In breast tumors, somatic mutation frequencies in TP53 and PIK3CA vary by tumor subtype and ancestry. Emerging data suggest tumor mutation status is associated with germline variants and genetic ancestry. We aimed to identify germline variants that are associated with somatic TP53 or PIK3CA mutation status in breast tumors.

Mentoring Minority Cancer Researchers of Tomorrow: Comparison of the Face-to-Face, Virtual, and Hybrid Training Methods of the CaRE Summer Cancer Research Education and Training Program.

In our previous publication, we reported a framework to develop an undergraduate cancer research training program at Florida A&M University (FAMU) under the umbrella of the Florida-California Cancer Research, Education, and Engagement (CaRE) Health Equity Center activity by harnessing the resources available at FAMU, the University of Florida (UF), and the University of Southern California (USC) Cancer Centers. The implementation of the CaRE face-to-face training platform was dramatically affected by the COVID-19 pandemic during the summer of 2020 and 2021 training periods. However, a concerted effort was made to restructure the face-to-face training model into virtual and hybrid training methods to maintain the continuity of the program during the pandemic.

Association of germline variants with somatic variants in breast tumors in a genome-wide study.

Background: In breast tumors, somatic mutation frequencies in and vary by tumor subtype and ancestry. HER2 positive and triple negative breast cancers (TNBC) have a higher frequency of somatic mutations than other subtypes. mutations are more frequently observed in hormone receptor positive tumors.

Exploring the genetic and molecular basis of differences in multiple myeloma of individuals of African and European descent.

Multiple Myeloma is a typical example of a neoplasm that shows significant differences in incidence, age of onset, type, and frequency of genetic alterations between patients of African and European ancestry. This perspective explores the hypothesis that both genetic polymorphisms and spontaneous somatic mutations in the TP53 tumor suppressor gene are determinants of these differences. In the US, the rates of occurrence of MM are at least twice as high in African Americans (AA) as in Caucasian Americans (CA).

Florida-California Cancer Research, Education and Engagement (CaRE) Health Equity Center: Structure, Innovations, and Initial Outcomes.

Introduction: The Florida-California Cancer Research, Education, and Engagement (CaRE) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE triad partnership.

Methods: CaRE serves diverse populations in Florida and California using a "molecule to the community and back" model.

Validation of Myc-Associated Protein X (MAX) regulation in growth hormone secreting and nonfunctional pituitary adenoma.

Introduction: Many patients with growth hormone-secreting pituitary adenoma (GHPA) fail to achieve biochemical remission, warranting investigation into epigenetic and molecular signatures associated with tumorigenesis and hormonal secretion. Prior work exploring the DNA methylome showed Myc-Associated Protein X (MAX), a transcription factor involved in cell cycle regulation, was differentially methylated between GHPA and nonfunctional pituitary adenoma (NFPA). We aimed to validate the differential DNA methylation and related MAX protein expression profiles between NFPA and GHPA.

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry.

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.

Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.

Design, Setting, And Participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.

Priorities to Promote Participant Engagement in the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network.

Background: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers.

Spatial Transcriptomic Analysis of a Diverse Patient Cohort Reveals a Conserved Architecture in Triple-Negative Breast Cancer.

Unlabelled: Triple-negative breast cancer (TNBC) is an aggressive disease that disproportionately affects African American (AA) women. Limited targeted therapeutic options exist for patients with TNBC. Here, we employ spatial transcriptomics to interrogate tissue from a racially diverse TNBC cohort to comprehensively annotate the transcriptional states of spatially resolved cellular populations.

African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Unlabelled: Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.

Analysis of the genomic landscapes of Barbadian and Nigerian women with triple negative breast cancer.

Purpose: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects women of African ancestry (WAA) and is often associated with poor survival. Although there is a high prevalence of TNBC across West Africa and in women of the African diaspora, there has been no comprehensive genomics study to investigate the mutational profile of ancestrally related women across the Caribbean and West Africa.

Methods: This multisite cross-sectional study used 31 formalin-fixed paraffin-embedded (FFPE) samples from Barbadian and Nigerian TNBC participants.

Wild-Type KRAS Allele Effects on Druggable Targets in KRAS Mutant Lung Adenocarcinomas.

mutations are one of the most common oncogenic drivers in non-small cell lung cancer (NSCLC) and in lung adenocarcinomas in particular. Development of therapeutics targeting KRAS has been incredibly challenging, prompting indirect inhibition of downstream targets such as MEK and ERK. Such inhibitors, unfortunately, come with limited clinical efficacy, and therefore the demand for developing novel therapeutic strategies remains an urgent need for these patients.

Analysis of Population Differences in Digital Conversations About Cancer Clinical Trials: Advanced Data Mining and Extraction Study.

Background: Racial and ethnic diversity in clinical trials for cancer treatment is essential for the development of treatments that are effective for all patients and for identifying potential differences in toxicity between different demographics. Mining of social media discussions about clinical trials has been used previously to identify patient barriers to enrollment in clinical trials; however, a comprehensive breakdown of sentiments and barriers by various racial and ethnic groups is lacking.

Objective: The aim of this study is to use an innovative methodology to analyze web-based conversations about cancer clinical trials and to identify and compare conversation topics, barriers, and sentiments between different racial and ethnic populations.

Multi-omic molecular profiling guide's efficacious treatment selection in refractory metastatic breast cancer: a prospective phase II clinical trial.

This prospective phase II clinical trial (Side Out 2) explored the clinical benefits of treatment selection informed by multi-omic molecular profiling (MoMP) in refractory metastatic breast cancers (MBCs). Core needle biopsies were collected from 32 patients with MBC at trial enrollment. Patients had received an average of 3.

Comprehensive molecular profiling of UV-induced metastatic melanoma in Nme1/Nme2-deficient mice reveals novel markers of survival in human patients.

Hepatocyte growth factor-overexpressing mice that harbor a deletion of the Ink4a/p16 locus (HP mice) form melanomas with low metastatic potential in response to UV irradiation. Here we report that these tumors become highly metastatic following hemizygous deletion of the Nme1 and Nme2 metastasis suppressor genes (HPN mice). Whole-genome sequencing of melanomas from HPN mice revealed a striking increase in lung metastatic activity that is associated with missense mutations in eight signature genes (Arhgap35, Atp8b4, Brca1, Ift172, Kif21b, Nckap5, Pcdha2, and Zfp869).