Rate of Pathogenic Germline Variants in Patients With Lung Cancer.

Purpose: Germline genetic testing (GGT) is now recommended for all patients diagnosed with ovarian or pancreatic cancer and for a large proportion of patients based solely on a diagnosis of colorectal or breast cancer. However, GGT is not yet recommended for all patients diagnosed with lung cancer (LC), primarily because of a lack of evidence that supports a significant frequency of identifying pathogenic germline variants (PGVs) in these patients. This study characterizes GGT results in a cohort of patients with LC.

Germline Pathogenic Variant Prevalence Among Latin American and US Hispanic Individuals Undergoing Testing for Hereditary Breast and Ovarian Cancer: A Cross-Sectional Study.

Purpose: To report on pathogenic germline variants detected among individuals undergoing genetic testing for hereditary breast and/or ovarian cancer (HBOC) from Latin America and compare them with self-reported Hispanic individuals from the United States.

Methods: In this cross-sectional study, unrelated individuals with a personal/family history suggestive of HBOC who received clinician-ordered germline multigene sequencing were grouped according to the location of the ordering physician: group A, Mexico, Central America, and the Caribbean; group B, South America; and group C, United States with individuals who self-reported Hispanic ethnicity. Relatives who underwent cascade testing were analyzed separately.

Unexpected actionable genetic variants revealed by multigene panel testing of patients with uterine cancer.

Objective: Hereditary uterine cancer (UC) is traditionally associated with pathogenic/likely pathogenic germline variants (PGVs) in Lynch syndrome genes or PTEN; however, growing evidence supports a role for other genes that may reveal new clinical management options. In this study we assessed the prevalence and potential clinical impact of PGVs identified in UC patients referred for comprehensive germline genetic testing that combined testing for Lynch syndrome, PTEN, and other cancer predisposition genes.

Methods: Prevalence of PGVs in patients referred to a single clinical lab for germline genetic testing with an indication of uterine or endometrial cancer were retrospectively assessed and compared by syndrome type, patient age at testing, and self-reported ancestry.

Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond and in Breast and Ovarian Cancer Patients.

Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in , , and other DNA damage repair (DDR) genes beyond or . We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.

Underdiagnosis of Hereditary Colorectal Cancers Among Medicare Patients: Genetic Testing Criteria for Lynch Syndrome Miss the Mark.

Purpose: Strict clinical criteria used by Medicare for germline testing for Lynch syndrome (LS) could lead to missed diagnoses of hereditary cancer syndromes given variable individual and family phenotypes. The aim of this study was to compare rates and spectrum of pathogenic or likely pathogenic (P/LP) variants in LS and other hereditary cancer genes on the basis of meeting Medicare LS testing criteria.

Methods: Retrospective review of Medicare beneficiaries who had multigene panel testing with an indication of personal or family history of colorectal cancer (CRC) was performed.

Yield and Utility of Germline Testing Following Tumor Sequencing in Patients With Cancer.

Importance: Both germline genetic testing and tumor DNA sequencing are increasingly used in cancer care. The indications for testing and utility of these 2 tests differ, and guidelines recommend that germline analysis follow tumor sequencing in certain patients to determine whether particular variants are of somatic or germline origin. Broad clinical experience with such follow-up testing has not yet been thoroughly described.

Loss-of-function variants in CTNNA1 detected on multigene panel testing in individuals with gastric or breast cancer.

Purpose: CTNNA1 is a potential diffuse gastric cancer risk gene, however CTNNA1 testing on multigene panel testing (MGPT) remains unstudied.

Methods: De-identified data from 151,425 individuals who underwent CTNNA1 testing at a commercial laboratory between October 2015 and July 2019 were reviewed. Tissue α-E-catenin immunohistochemistry was performed on CTNNA1 c.

Prevalence of Germline Variants in Prostate Cancer and Implications for Current Genetic Testing Guidelines.

Importance: Prostate cancer is the third leading cause of cancer-related death in men in the United States. Although serious, most of these diagnoses are not terminal. Inherited risk for prostate cancer is associated with aggressive disease and poorer outcomes, indicating a critical need for increased genetic screening to identify disease-causing variants that can pinpoint individuals at increased risk for metastatic castration-resistant prostate cancer.

Underdiagnosis of Hereditary Breast and Ovarian Cancer in Medicare Patients: Genetic Testing Criteria Miss the Mark.

Background: An estimated 5-10% of breast and ovarian cancers are due to hereditary causes such as hereditary breast and ovarian cancer (HBOC) syndrome. Medicare, the third-party payer that covers 44 million patients in the United States, has implemented a set of clinical criteria to determine coverage for the testing of the BRCA1 and BRCA2 genes. These criteria, developed to identify carriers of BRCA1/2 variants, have not been evaluated in the panel testing era.

Expanded Gene Panel Use for Women With Breast Cancer: Identification and Intervention Beyond Breast Cancer Risk.

Background: Clinicians ordering multi-gene next-generation sequencing panels for hereditary breast cancer risk have a variety of test panel options. Many panels include lesser known breast cancer genes or genes associated with other cancers. The authors hypothesized that using broader gene panels increases the identification of clinically significant findings, some relevant and others incidental to the testing indication.

Germline hemizygous deletion of locus in a patient presenting with Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome usually associated with germline alterations. Its genetic basis in wild-type pedigrees is less understood. Using whole-genome sequencing, we identified a germline hemizygous deletion ablating in a wild-type patient presenting with high-grade sarcoma, laryngeal squamous cell carcinoma and a family history suggestive of LFS.

Costs and consequences of comprehensive stillbirth assessment.

Objective: The purpose of this study was to determine the consequences and costs of comprehensive stillbirth assessment.

Study Design: Through reconstruction, we determined what consequences arise from assessment in the first 1477 stillborn pregnancies that were referred to the Wisconsin Stillbirth Service Program. Economic costs of stillbirth assessment were derived from real-time studies of those who performed the analyses and the costs of materials that were consumed.