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1.
Gynecol Oncol ; 180: 35-43, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38041901

RESUMO

OBJECTIVE: To define molecular features of ovarian cancer (OC) with germline pathogenic variants (PVs) in non-BRCA homologous recombination (HR) genes and analyze survival compared to BRCA1/2 and wildtype (WT) OC. METHODS: We included patients with OC undergoing tumor-normal sequencing (MSK-IMPACT) from 07/01/2015-12/31/2020, including germline assessment of BRCA1/2 and other HR genes ATM, BARD1, BRIP1, FANCA, FANCC, NBN, PALB2, RAD50, RAD51B, RAD51C, and RAD51D. Biallelic inactivation was assessed within tumors. Progression-free (PFS) and overall survival (OS) were calculated from pathologic diagnosis using the Kaplan-Meier method with left truncation. Whole-exome sequencing (WES) was performed in a subset. RESULTS: Of 882 patients with OC, 56 (6.3%) had germline PVs in non-BRCA HR genes; 95 (11%) had BRCA1-associated OC (58 germline, 37 somatic); and 59 (6.7%) had BRCA2-associated OC (40 germline, 19 somatic). High rates of biallelic alterations were observed among germline PVs in BRIP1 (11/13), PALB2 (3/4), RAD51B (3/4), RAD51C (3/4), and RAD51D (8/10). In cases with WES (27/35), there was higher tumor mutational burden (TMB; median 2.5 [1.1-6.0] vs. 1.2 mut/Mb [0.6-2.6]) and enrichment of HR-deficient (HRD) mutational signatures in tumors associated with germline PALB2 and RAD51B/C/D compared with BRIP1 PVs (p < 0.01). Other features of HRD, including telomeric-allelic imbalance (TAI) and large-scale state transitions (LSTs), were similar. Although there was heterogeneity in PFS/OS by gene group, only BRCA1/2-associated OC had improved survival compared to WT OC (p < 0.01). CONCLUSIONS: OCs associated with germline PVs in non-BRCA HR genes represent a heterogenous group, with PALB2 and RAD51B/C/D associated with an HRD phenotype.


Assuntos
Proteína BRCA1 , Neoplasias Ovarianas , Humanos , Feminino , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ovarianas/patologia , Mutação em Linhagem Germinativa , Recombinação Homóloga , Fenótipo , Células Germinativas/patologia , Predisposição Genética para Doença
2.
J Urol ; 209(5): 918-927, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36974724

RESUMO

PURPOSE: Genetic testing may alter clinical management for individuals with metastatic prostate cancer by identifying additional therapies. Traditional counseling models are unlikely to enable time-sensitive therapeutic decision-making. This study aimed to determine the feasibility and clinical impact of an alternative hereditary genetic testing model. MATERIALS AND METHODS: As part of a multicenter, single-arm prospective trial, individuals with advanced prostate cancer were referred by their oncologist for testing of 14 genes associated with hereditary prostate cancer. Pretest education (brochure and video) was provided in the oncology clinic. Questionnaires assessing participant satisfaction with both pretest education and decision to undergo genetic testing were collected. A genetic counselor contacted participants by phone to obtain family history and discuss results. Medical records were queried to determine whether a change in clinical management was discussed. RESULTS: Of 501 participants consented to germline analysis, 51 (10.2%) had at least 1 pathogenic/likely pathogenic variant. Change in treatment was discussed with 22/48 (45.8%) of eligible participants who tested positive. Feasibility of this model was assessed by participant satisfaction and turnaround time. Average±SD satisfaction with the pretest education (15.5±2.2, 4-20 scale) and with the decision to undergo genetic testing (17.1±2.9, 4-20 scale) were both high. Results were returned 20 days (median) after sample collection. CONCLUSIONS: Oncologist-initiated germline genetic testing in collaboration with a genetic counselor is a feasible approach to testing advanced prostate cancer patients with impactful clinical actionability. The testing model and educational material serve as resources to clinicians treating prostate cancer patients.


Assuntos
Testes Genéticos , Neoplasias da Próstata , Masculino , Humanos , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Aconselhamento Genético , Aconselhamento
3.
Genet Med ; 24(12): 2587-2590, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36222830

RESUMO

PURPOSE: With the recent guideline change for individuals at average risk for colorectal cancer (CRC) to initiate colonoscopy at the age of 45 years, there is a need to provide an updated counseling framework for individuals with variants in moderate-penetrance CRC susceptibility genes. METHODS: Population age-specific incidence rates for CRC were obtained from the 2014-2018 US Surveillance, Epidemiology, and End Results Program cancer statistics. Average-risk multipliers derived from a systematic meta-analysis were used to calculate the 5-year and cumulative lifetime risks for specific genetic variants associated with a moderate risk for CRC: NM_007194.4(CHEK2):c.1100del (p.Thr367fs), NM_007194.4(CHEK2):c.470T>C (p.Ile157Thr), NM_000038.6(APC):c.3920T>A (p.Ile1307Lys) and monoallelic MUTYH. RESULTS: When an individual at average risk would initiate colonoscopy at age 45 years, a CRC risk of 0.39% is reached. For CHEK2 1100delC, CHEK2 I157T, and APC I1307K heterozygotes, this same level of risk is reached (or nearly reached) by age 40 to 45 years. For individuals with a monoallelic MUTYH variant, the CRC risk is 0.46% by age 45 to 49 years, similar to individuals at average risk. CONCLUSION: These updated calculations support recommendations to initiate earlier colonoscopy surveillance for CHEK2 and APC I1307K germline variant heterozygotes. However, earlier surveillance is not indicated for individuals with monoallelic MUTYH germline variants in the absence of family history.


Assuntos
Neoplasias Colorretais , Aconselhamento Genético , Predisposição Genética para Doença , Adulto , Humanos , Pessoa de Meia-Idade , Quinase do Ponto de Checagem 2/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Heterozigoto , Penetrância
4.
JCO Oncol Pract ; 18(4): e462-e471, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34652959

RESUMO

PURPOSE: With onset of the COVID-19 pandemic, telehealth became the primary modality for health care appointments. This study examined patient experiences with and preferences for telehealth at a cancer genetic counseling clinic throughout the first 6 months of the pandemic (March-August 2020). METHODS: An anonymous survey assessed patient demographics; usage and prior experience with technology; emotional responses, technical experiences, and satisfaction with the telehealth appointment (via the Genetic Counseling Satisfaction Scale and Visit-Specific Satisfaction Questionnaire); preference for future telehealth; and recommendation of telehealth to others. RESULTS: Among 380 respondents, most were highly satisfied with the telehealth appointment (with 65.6% and 66.4% of participants completing the Genetic Counseling Satisfaction Scale and Visit-Specific Satisfaction Questionnaire, respectively). Multivariable analyses indicated several notable findings. Adjusting for relevant covariates, participants with less education felt significantly more concerned about telehealth than those with highest educational attainment. Participants age 40-69 years were generally more comfortable, relieved, and grateful that their appointment was scheduled as telehealth than were those older than 70 years. Women were marginally more relieved and grateful for telehealth appointments than men. As the pandemic progressed, significantly more participants were highly satisfied with their telehealth appointment and participants trended toward having greater preferences for future telehealth use. Most participants (78.6%) would recommend telehealth to others, although 50.8% preferred future in-person appointments. CONCLUSION: As the pandemic progressed, patients expressed increasing preferences for and satisfaction with telehealth. Service delivery models that incorporate individual patient preferences should be developed with special consideration to factors such as age, sex, and education level.


Assuntos
COVID-19 , Neoplasias , Telemedicina , Adulto , Idoso , COVID-19/epidemiologia , Feminino , Aconselhamento Genético , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , Preferência do Paciente , SARS-CoV-2
5.
Clin Genet ; 101(2): 161-182, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34355387

RESUMO

Li-Fraumeni syndrome (LFS), a rare cancer predisposition syndrome caused by germline mutations in the TP53 gene, is associated with significant lifetime risk of developing cancer and warrants extensive and long-term surveillance. There are psychosocial impacts on individuals and families living with this condition, from the initial diagnosis throughout multiple stages across the lifespan, but these impacts have not been systematically reviewed and organized. The objective of this scoping review was to synthesize and characterize the literature on psychosocial screening and outcomes, educational needs, support services, and available interventions for patients and families with LFS. A systematic search of six databases was most recently conducted in August 2020: (PubMed/MEDLINE (NLM), EMBASE (Elsevier), Cochrane Library (Wiley), CINAHL (EBSCO), PsycINFO (OVID), and Web of Science (Clarivate Analytics). A total of 15 757 titles were screened, and 24 articles included. Several important themes were identified across studies: factors associated with TP53 genetic testing, LFS surveillance, psychological outcomes, and communication. Findings related to these themes were organized into age-specific categories (age agnostic/across the lifespan, childhood, adolescence and young adulthood, and adulthood).


Assuntos
Cuidadores/psicologia , Necessidades e Demandas de Serviços de Saúde , Síndrome de Li-Fraumeni/psicologia , Intervenção Psicossocial , Fatores Etários , Gerenciamento Clínico , Genes p53 , Predisposição Genética para Doença , Testes Genéticos , Humanos , Síndrome de Li-Fraumeni/diagnóstico , Síndrome de Li-Fraumeni/etiologia , Síndrome de Li-Fraumeni/terapia , Intervenção Psicossocial/métodos , Vigilância em Saúde Pública , Apoio Social
6.
Am J Med Genet C Semin Med Genet ; 187(1): 28-36, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33225573

RESUMO

The COVID-19 pandemic disrupted the delivery of healthcare services, including genetic counseling. This study assessed the professional impact of the pandemic on genetic counselors (GCs) and evaluated how genetics service delivery models changed in New York State (NYS). One hundred sixty-five NYS GCs participated in an anonymous survey. Clinic structure, telegenetics (video and/or telephone consultations) use and acceptability, and professional practices before and during the pandemic were compared. The most frequently reported consultation type shifted from in-person only (49%) before the pandemic to telegenetics only (39%) during. Most were satisfied with video (93.1%) and telephone (81.4%) telegenetics. Additionally, 93.5% of participants expressed a desire to continue using telegenetics after the pandemic resolves. Common obstacles included difficulties coordinating sample collection (60.2%) and obtaining written consent for testing (57.6%). Billing methods for consultations during the pandemic did not change significantly. Participants were asked about NYS's lack of licensure, which restricts billing options. Most felt that genetic counseling licensure would benefit the profession (92.6%), the public (88.5%), and their institution/company (74.5%). This study provides insight into the effects of the rapid adoption of telegenetics and can guide future discussions about best practices for its use even after the health crisis resolves.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Aconselhamento Genético , SARS-CoV-2 , Atenção à Saúde , Pessoal de Saúde , Humanos , New York/epidemiologia , Pandemias , Percepção , Vigilância em Saúde Pública , Encaminhamento e Consulta , Telemedicina
7.
Mol Genet Genomic Med ; 8(8): e1293, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32463173

RESUMO

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), caused by heterozygous germline pathogenic variants in the FH, confers an increased risk for cutaneous and uterine leiomyomas and renal cancer. METHODS: About 13,722 advanced cancer patients, including 560 with renal cell carcinoma, had germline analysis performed in the context of tumor-normal sequencing under an IRB approved protocol. RESULTS: We report two unrelated individuals with early onset kidney cancer who both carried the c.914C > T (p.Phe305Ser) germline variant in the FH. Both tumors exhibited loss of FH staining by immunohistochemistry and/or positive 2SC staining. Subsequent familial testing discovered that a daughter of a proband who carried the variant had both cutaneous and uterine leiomyomas. CONCLUSION: This combination of evidence suggests that the FH c.914C > T (p.Phe305Ser) is pathogenic for HLRCC.


Assuntos
Fumarato Hidratase/genética , Leiomiomatose/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Cutâneas/genética , Neoplasias Uterinas/genética , Feminino , Mutação em Linhagem Germinativa , Humanos , Leiomiomatose/patologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Síndromes Neoplásicas Hereditárias/patologia , Linhagem , Neoplasias Cutâneas/patologia , Neoplasias Uterinas/patologia
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