Variable Genomic Landscapes of Advanced Melanomas with Heavy Pigmentation.

Background: In the current study, we examined the real-world prevalence of highly pigmented advanced melanomas (HPMel) and the clinicopathologic, genomic, and ICPI biomarker signatures of this class of tumors.

Materials And Methods: Our case archive of clinical melanoma samples for which the ordering physician requested testing for both PD-L1 immunohistochemistry (IHC) and comprehensive genomic profiling (CGP) was screened for HPMel cases, as well as for non-pigmented or lightly pigmented advanced melanoma cases (LPMel).

Results: Of the 1268 consecutive melanoma biopsies in our archive that had been submitted for PD-L1 IHC, 13.

HPV51-associated Leiomyosarcoma: A Novel Class of TP53/RB1-Wildtype Tumor With Predilection for the Female Lower Reproductive Tract.

Inactivating mutations in tumor suppressor genes TP53 and RB1 are considered central drivers in leiomyosarcomas (LMSs). In high-risk human papillomavirus (HPV)-related tumors, a similar functional outcome is achieved through oncoproteins E6 and E7, which inactivate the p53 and RB1 proteins, respectively. Here, we hypothesized that HPV infection could provide an alternative mechanism for tumorigenesis in a subset of TP53/RB1-wildtype LMS.

Molecular analysis of endometrial serous carcinoma reveals distinct clinicopathologic and genomic subgroups.

Objectives: Endometrial serous carcinoma (EMSC) is an aggressive variant of uterine cancer with limited therapeutic options. We sought to define distinct clinicopathologic and genomic EMSC subgroups.

Methods: We retrospectively analyzed 2159 EMSC and 2346 endometrioid-type endometrial carcinomas (EEC) tissue specimens that had undergone comprehensive genomic profiling (CGP) via the FoundationOne CDx assay during routine clinical care.

A Review on the Surgical Management of Insular Gliomas.

The surgical treatment of insular gliomas requires specialized knowledge. Over the last three decades, increased momentum in surgical resection of insular gliomas shifted the focus from one of expectant management to maximal safe resection to establish a diagnosis, characterize tumor genetics, treat preoperative symptoms (i.e.

Circulating Cell-Free DNA Yield and Circulating-Tumor DNA Quantity from Liquid Biopsies of 12 139 Cancer Patients.

Background: The amounts of circulating cell-free DNA (cfDNA) and circulating-tumor DNA (ctDNA) present in peripheral blood liquid biopsies can vary due to preanalytic/analytic variables. In this study, we examined the impact of patient age, sex, stage, and tumor type on cfDNA yield, ctDNA fraction, and estimated ctDNA quantity from a large cohort of clinical liquid biopsy samples.

Methods: We performed a retrospective analysis of 12 139 consecutive samples received for liquid biopsy (FoundationOne® Liquid) clinical testing.

Myocardial Function in Premenopausal Women Treated With Ovarian Function Suppression and an Aromatase Inhibitor.

Background: Premenopausal women with high-risk hormone receptor (HR)-positive breast cancer often receive ovarian function suppression (OFS) with aromatase inhibitor therapy; however, abrupt menopause induction, together with further decrements in estrogen exposure through aromatase inhibition, may affect cardiovascular microcirculatory function. We examined adenosine-induced changes in left ventricular (LV) myocardial T1, a potential subclinical marker of LV microcirculatory function in premenopausal women undergoing treatment for breast cancer.

Methods: Twenty-one premenopausal women (14 with HR-positive breast cancer receiving OFS with an aromatase inhibitor and 7 comparator women with triple-negative breast cancer [TNBC] who had completed primary systemic therapy) underwent serial resting and adenosine cardiovascular magnetic resonance imaging measurements of LV myocardial T1 and LV volumes, mass, and ejection fraction.

Clinicopathological and genomic characterization of BCORL1-driven high-grade endometrial stromal sarcomas.

BCORL1 is a transcriptional corepressor homologous to BCOR. We describe 12 BCORL1-altered uterine sarcomas with striking resemblance to BCOR-altered endometrial stromal sarcoma (BCOR-ESS), including 5 with BCORL1 rearrangements (JAZF1-BCORL1, EP300-BCORL1, or internal BCORL1 rearrangement), 5 with inactivating BCORL1 mutations (T513fs*22, P600fs*1, R945*, R1196*, or R1265fs*4) and 2 with homozygous BCORL1 deletion. The median patient age was 57.

Pan-cancer analysis of (PD-L1) mutations in 314,631 patient samples and subset correlation with PD-L1 protein expression.

Background: The effects of non-amplification short variant (SV) mutations in (programmed death-ligand 1 (PD-L1)) on PD-L1 protein expression and immune checkpoint inhibitors (ICPIs) therapy are unknown. Here, we present a retrospective analysis of mutations detected by comprehensive genomic profiling (CGP) and correlate these results with tumor-cell PD-L1 immunohistochemistry (IHC)-based expression assessment to better understand the relationship between mutations and protein expression of PD-L1.

Methods: CGP was performed on hybridization-captured, adaptor ligation-based libraries using DNA and/or RNA extracted from 314,631 tumor samples that were sequenced for up to 406 cancer-related genes and select gene rearrangements.

JAK2 Rearrangements Are a Recurrent Alteration in CD30+ Systemic T-Cell Lymphomas With Anaplastic Morphology.

Peripheral T-cell lymphoma (PTCL) comprises a heterogenous group of rare mature T-cell neoplasms. While some PTCL subtypes are well-characterized by histology, immunophenotype, and recurrent molecular alterations, others remain incompletely defined. In particular, the distinction between CD30+ PTCL, not otherwise specified and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma can be subject to disagreement.

Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases.

Background: Among patients with breast carcinoma who have metastatic disease, 15%-30% will eventually develop brain metastases. We examined the genomic landscape of a large cohort of patients with breast carcinoma brain metastases (BCBMs) and compared it with a cohort of patients with primary breast carcinomas (BCs).

Material And Methods: We retrospectively analyzed 733 BCBMs tested with comprehensive genomic profiling (CGP) and compared them with 10,772 primary breast carcinomas (not-paired) specimens.

Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma.

Background: Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell histiocytosis and Erdheim-Chester disease have been well described, other less common and often aggressive tumors in this broad category remain poorly characterized, and comparison studies across the World Health Organization diagnostic categories are lacking.

Methods: Tumor samples from a total of 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs), underwent hybridization capture with analysis of up to 406 cancer-related genes.

FoundationOne CDx testing accurately determines whole arm 1p19q codeletion status in gliomas.

Background: Molecular profiling of gliomas is vital to ensure diagnostic accuracy, inform prognosis, and identify clinical trial options for primary and recurrent tumors. This study aimed to determine the accuracy of reporting the whole arm 1p19q codeletion status from the FoundationOne platform.

Methods: Testing was performed on glioma samples as part of clinical care and analyzed up to 395 cancer-associated genes (including ).

Clinicopathologic and Genomic Characterization of PD-L1 Positive Urothelial Carcinomas.

Introduction: Pembrolizumab was approved with an accompanying companion diagnostic (CDx) assay (PD-L1 DAKO 22C3) for urothelial carcinoma (UC). In this study, we further characterize the clinicopathologic and genomic features of UC that are programmed death-ligand 1 (PD-L1) positive.

Materials And Methods: The cohort of this study consisted of a total of 528 consecutive UC patients with PD-L1 immunohistochemistry (IHC) and comprehensive genomic profiling (CGP).

Clinicopathologic and genomic characterization of PD-L1-positive uterine cervical carcinoma.

Positive program death-ligand 1 (PD-L1) immunohistochemistry (IHC) is an approved companion diagnostic guiding the use of immune checkpoint inhibitors in uterine cervical carcinoma (CXC). The clinical and genomic features of PD-L1-positive (PD-L1) CXC have not been previously described. We reviewed the clinicopathologic and molecular features of 647 CXC cases that were tested using DAKO 22C3 PD-L1 IHC and comprehensive genomic profiling during the course of clinical care.

Immunophenotype of Vestibular Schwannomas.

Background: Vestibular schwannomas exhibit a uniquely variable natural history of growth, stability, or even spontaneous regression. We hypothesized that a transitory population of immune cells, or immunomodulation of tumors cells, may influence the growth pattern of schwannomas. We therefore sought to characterize the impact of the immune microenvironment on schwannoma behavior.

Predictive Biomarkers for Immune Checkpoint Inhibitors in Metastatic Breast Cancer.

We examined a large dataset of female metastatic breast cancers (MBCs) profiled with comprehensive genomic profiling (CGP) to identify the prevalence and distribution of immunotherapy responsiveness-associated biomarkers. DNA was extracted from 3831 consecutive MBCs: 1237 (ER /HER2 ), 1953 ER /HER2 , and 641 triple-negative breast cancer (TNBC). CGP was performed using the FoundationOne or FoundationOne CDx NGS assay.

New cancer therapies. Are haematopoietic cell transplants a dead duck?

Recent therapy advances for haematological cancers including new drugs and targeted and immune therapies raise the question whether there is a future for haematopoietic cell transplants. Although encouraging, the survival improvements achieved with these new modalities in persons who might otherwise receive a transplant are modest. Furthermore, these modalities are likely to be complementary, not competitive.

Distinct genomic subclasses of high-grade/progressive meningiomas: NF2-associated, NF2-exclusive, and NF2-agnostic.

Background: Genomic studies of high-grade/progressive meningiomas have reported a heterogeneous mutation spectrum, identifying few recurrently mutated genes. Most studies have been underpowered to detect genomic subclasses of aggressive meningiomas due to relatively small number of available samples. Here, we present a genomic survey of one of the largest multi-institutional cohorts of high-grade/progressive meningiomas to date.

Recurrent urothelial carcinoma-like FGFR3 genomic alterations in malignant Brenner tumors of the ovary.

Malignant Brenner tumor is a rare primary ovarian carcinoma subtype that may present diagnostic and therapeutic conundrums. Here, we characterize the genomics of 11 malignant Brenner tumors, which represented 0.1% of 14,153 clinically advanced ovarian carcinomas submitted for genomic profiling during the course of clinical care.

Molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian origin.

Mesonephric carcinoma is a rare cancer that most often arises within the cervix, and less frequently, in the ovary and endometrium. A retrospective search of our CLIA-certified and CAP-accredited reference molecular laboratory database (Foundation Medicine, Inc.) identified 20 mesonephric or mesonephric-like, cervical (n = 10), endometrial (n = 5), ovarian (n = 4) or peri-bladder (n = 1) carcinomas that had undergone comprehensive genomic profiling via next generation sequencing.

-Null Leiomyosarcoma: A Novel, Genomically Distinct Class of /-Wild-Type Tumor With Frequent Genomic Alterations and 1p/19q-Codeletion.

Purpose: Leiomyosarcoma (LMS) harbors frequent mutations in and but few actionable genomic alterations. Here, we searched for recurrent actionable genomic alterations in LMS that occur in the absence of common untreatable oncogenic drivers.

Methods: Tissues from 276,645 unique advanced cancers, including 2,570 uterine and soft tissue LMS, were sequenced by hybrid-capture-based next-generation DNA and RNA sequencing/comprehensive genomic profiling of up to 406 genes.

Promoting Active Aging: Lessons Learned in an Implementation Pilot in Primary Care.

Background: Physical activity (PA) preserves mobility, but few practices screen older adults for mobility impairment or counsel on PA.

Design: "Promoting Active Aging" (PAA) was a mixed-methods randomized-controlled pilot, to test the feasibility and acceptability of a video-based PA counseling tool and implementation into practice of two mobility assessment tools.

Setting: Three primary care practices affiliated with Wake Forest Baptist Health.