Search Our Scientific Publications & Authors

Publications
find publications by category +
Translate page:

Moderate penetrance genes complicate genetic testing for breast cancer diagnosis: ATM, CHEK2, BARD1 and RAD51D.

Authors:
R Graffeo H Q Rana F Conforti B Bonanni M J Cardoso S Paluch-Shimon O Pagani A Goldhirsch A H Partridge M Lambertini J E Garber

Breast 2022 Jun 18;65:32-40. Epub 2022 Jun 18.

Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, USA.

Breast cancer risk associated with germline likely pathogenic/pathogenic variants (PV) varies by gene, often by penetrance (high >50% or moderate 20-50%), and specific locus. Germline PVs in BRCA1 and BRCA2 play important roles in the development of breast and ovarian cancer in particular, as well as in other cancers such as pancreatic and prostate cancers and melanoma. Recent studies suggest that other cancer susceptibility genes, including ATM, CHEK2, PALB2, RAD51C and RAD51D confer differential risks of breast and other specific cancers. In the era of multigene panel testing, advances in next-generation sequencing technologies have notably reduced costs in the United States (US) and enabled sequencing of BRCA1/2 concomitantly with additional genes. The use of multigene-panel testing is beginning to expand in Europe as well. Further research into the clinical implications of variants in moderate penetrance genes, particularly in unaffected carriers, is needed for appropriate counselling and risk management with data-driven plans for surveillance and/or risk reduction. For individuals at high risk without any pathogenic or likely pathogenic variant in cancer susceptibility genes or some carriers of pathogenic variants in moderate-risk genes such as ATM and CHEK2, polygenic risk scores offer promise to help stratify breast cancer risk and guide appropriate risk management options. Cancer patients whose tumours are driven by the loss of function of both copies of a predisposition gene may benefit from therapies targeting the biological alterations induced by the dysfunctional gene e.g. poly ADP ribose polymerase (PARP) inhibitors and other novel pathway agents in cancers with DNA repair deficiencies. A better understanding of mechanisms by which germline variants drive various malignancies may lead to improvements in both therapeutic and preventive management options.

Download full-text PDF

 Source
http://dx.doi.org/10.1016/j.breast.2022.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253488PMC
June 2022

Publication Analysis

Top Keywords

atm chek2
12
breast cancer
12
cancer risk
8
moderate penetrance
8
susceptibility genes
8
management options
8
cancer susceptibility
8
penetrance genes
8
risk management
8
cancer
7
risk
7
genes
6
breast
5
data-driven plans
4
plans surveillance
4
surveillance and/or
4
risk reduction
4
management data-driven
4
counselling risk
4
and/or risk
4

Keyword Occurance

Similar Publications

Development and Validation of the PREMMplus Model for Multigene Hereditary Cancer Risk Assessment.

Authors:
Matthew B Yurgelun Hajime Uno C Sloane Furniss Chinedu Ukaegbu Miki Horiguchi Amal Yussuf Holly LaDuca Anu Chittenden Judy E Garber Sapna Syngal

J Clin Oncol 2022 Aug 12:JCO2200120. Epub 2022 Aug 12.

Dana-Farber Cancer Institute, Boston, MA.

Purpose: With the availability of multigene panel testing (MGPT) for hereditary cancer risk assessment, clinicians need to assess the likelihood of pathogenic germline variants (PGVs) across numerous genes in parallel. This study's aim was to develop and validate a clinical prediction model (PREMMplus) for MGPT risk assessment.

Materials And Methods: PREMMplus was developed in a single-institution cohort of 7,280 individuals who had undergone MGPT. Read More

View Article and Full-Text PDF
August 2022
Similar Publications

Hereditary Breast Cancer in the Brazilian State of Ceará (The CHANCE Cohort): Higher-Than-Expected Prevalence of Recurrent Germline Pathogenic Variants.

Authors:
Ana Carolina Leite Vieira Costa Gifoni Markus Andret Cavalcante Gifoni Camila Martins Wotroba Edenir Inez Palmero Eduardo Leite Vieira Costa Wellington Dos Santos Maria Isabel Achatz

Front Oncol 2022 22;12:932957. Epub 2022 Jul 22.

Oncology Center - Sirio Libanes Hospital, São Paulo, Brazil.

Purpose: There is a significant lack of epidemiological data on hereditary cancer in Northeast Brazil. This is the largest study on the prevalence and mutational spectrum of cancer predisposition genes conducted in this region and the first in the State of Ceará.

Methods: Patients ≥18 years of age that were referred to CHANCE (Grupo de Câncer Hereditário do Ceará) from March 2014 to December 2020 with testing criteria for breast cancer susceptibility genes according to NCCN v. Read More

View Article and Full-Text PDF
July 2022
Similar Publications

DNA damage repair genes alterations in genito-urinary malignancies.

Authors:
Charles Dariane Marc-Olivier Timsit

Eur Surg Res 2022 Aug 9. Epub 2022 Aug 9.

Background High-fidelity repair of DNA damage repair (DDR) [either single-strand- (SSBs) or double-strand breaks (DSBs)] is necessary for maintaining genomic integrity and cell survival. DDR alterations are commonly found in genito-urinary malignancies involving either DSBs repair by the homologous recombination repair (HRR) system (BRCA1/2 pathway) or the SSBs repair through the Poly-ADP-ribose polymerase (PARP) pathway. PARP inhibitors (PARPi) exploit defects in the DNA repair pathway through synthetic lethality, DSBs being repaired only in HR-proficient cells but not in HR-deficient (HRD) cells. Read More

View Article and Full-Text PDF
August 2022
Similar Publications

Fibroblast testing can inform medical management in individuals with mosaic variants detected on hereditary cancer panels.

Authors:
Erin G Sutcliffe Jessica L Mester Lisa R Susswein Maegan E Roberts Megan L Marshall Kathleen S Hruska

Cancer Genet 2022 Aug 28;266-267:86-89. Epub 2022 Jul 28.

GeneDx, Gaithersburg, MD, United States.

Mosaic variants are regularly detected on hereditary cancer genetic tests. While some of these variants may be constitutional, the majority are likely limited to blood lineages. In the present study, we correlate clinical histories from individuals with mosaic findings identified on hereditary cancer testing and the outcomes of follow-up fibroblast (FB) testing. Read More

View Article and Full-Text PDF
August 2022
Similar Publications

Integrated genomic sequencing in myeloid blast crisis chronic myeloid leukemia (MBC-CML), identified potentially important findings in the context of leukemogenesis model.

Authors:
Golnaz Ensieh Kazemi-Sefat Mohammad Keramatipour Mohammad Vaezi Seyed Mohsen Razavi Kaveh Kavousi Amin Talebi Shahrbanoo Rostami Marjan Yaghmaei Bahram Chahardouli Saeed Talebi Kazem Mousavizadeh

Sci Rep 2022 Jul 27;12(1):12816. Epub 2022 Jul 27.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

Chronic myeloid leukemia (CML) is a model of leukemogenesis in which the exact molecular mechanisms underlying blast crisis still remained unexplored. The current study identified multiple common and rare important findings in myeloid blast crisis CML (MBC-CML) using integrated genomic sequencing, covering all classes of genes implicated in the leukemogenesis model. Integrated genomic sequencing via Whole Exome Sequencing (WES), Chromosome-seq and RNA-sequencing were conducted on the peripheral blood samples of three CML patients in the myeloid blast crisis. Read More

View Article and Full-Text PDF
July 2022
Similar Publications
}