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

Graffeo, Rossella; Rana, Huma Q.; Conforti, Fabio; Bonanni, Bernardo; Cardoso, M.J.; Paluch‐Shimon, Shani; Pagani, Olivia; Goldhirsch, Aron; Partridge, Ann H.; Lambertini, Matteo; Garber, Judy E.

doi:10.1016/j.breast.2022.06.003

Cited by 40 publications

(13 citation statements)

References 72 publications

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“…Mutations and polymorphisms in them can lead to abnormal cell growth, which can lead to the development of cancer. Among the genes that are associated with the development and progression of breast cancer, the following are currently listed [ 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]: BRCA1 and BRCA2 genes, which have the best documented association with breast cancer; having a mutation in these genes is responsible for a 50–80% risk of breast cancer and a 45% risk of ovarian cancer before the age of 85—with a mutation in the BRCA1 gene and a 31–56% risk of breast cancer and 11–27% of ovarian cancer in BRCA2 mutation [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]; the PALB2 gene, which is responsible for the repair of damaged DNA; carriers of the defective gene have a 35% risk of developing breast cancer before the age of 70 [ 31 , 32 , 33 , 34 , 35 , 36 ]; the CHEK2 gene, which is responsible for the production of a protein that inhibits tumor growth; women with a mutation in this gene have a twice as high a risk of developing breast cancer compared to the general population [ 37 , 38 , 39 , 40 , 41 , 42 ]; the NBN gene, which encodes a protein regulating the DNA repair process and maintaining chromosome stability [ 43 , 44 , 45 , 46 , ...…”

Section: Introductionmentioning

confidence: 99%

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Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA

Szczepanek

Skorupa

Jarkiewicz‐Tretyn³

et al. 2023

IJMS

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Breast cancer exhibits various epigenetic abnormalities that regulate gene expression and contribute to tumor characteristics. Epigenetic alterations play a significant role in cancer development and progression, and epigenetic-targeting drugs such as DNA methyltransferase inhibitors, histone-modifying enzymes, and mRNA regulators (such as miRNA mimics and antagomiRs) can reverse these alterations. Therefore, these epigenetic-targeting drugs are promising candidates for cancer treatment. However, there is currently no effective epi-drug monotherapy for breast cancer. Combining epigenetic drugs with conventional therapies has yielded positive outcomes and may be a promising strategy for breast cancer therapy. DNA methyltransferase inhibitors, such as azacitidine, and histone deacetylase inhibitors, such as vorinostat, have been used in combination with chemotherapy to treat breast cancer. miRNA regulators, such as miRNA mimics and antagomiRs, can alter the expression of specific genes involved in cancer development. miRNA mimics, such as miR-34, have been used to inhibit tumor growth, while antagomiRs, such as anti-miR-10b, have been used to inhibit metastasis. The development of epi-drugs that target specific epigenetic changes may lead to more effective monotherapy options in the future.

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Section: Introductionmentioning

confidence: 99%

“…the CHEK2 gene, which is responsible for the production of a protein that inhibits tumor growth; women with a mutation in this gene have a twice as high a risk of developing breast cancer compared to the general population [ 37 , 38 , 39 , 40 , 41 , 42 ];…”

Section: Introductionmentioning

confidence: 99%

Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA

Szczepanek

Skorupa

Jarkiewicz‐Tretyn³

et al. 2023

IJMS

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“…Breast cancer is among the most common cancers with genetic susceptibility, and BRCA1 and BRCA2 are regarded as the most commonly mutated genes [3]. Besides BRCA1 and BRCA2, many high and moderate penetrance genes for breast-ovarian cancer, including TP53, CDH1, PALB2, STK11, PTEN, CHEK2, ATM, BARD1, BRIP1, and RAD51D, were identi ed after the advent of next-generation sequencing (NGS) [3][4][5]. Many studies have shown that non-BRCA cancer susceptibility genes contribute to increased breast and other cancer risk.…”

Section: Introductionmentioning

confidence: 99%

Germline mutations in hereditary breast-ovarian cancer spectrum in Thailand: Results from multi-gene panel testing in 4,567 Thai patients

Pithukpakorn,

Kansuttiviwat,

Lertwilaiwittaya

et al. 2023

Preprint

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Multi-gene panel testing has led to the detection of pathogenic/likely pathogenic (P/LP) variants in many cancer susceptibility genes in patients with breast-ovarian cancer spectrum. However, the clinical and genomic data of Asian populations including Thai cancer patients was underrepresented and the clinical significance of multi-gene panel testing in Thailand remains undetermined. In this study, we collected the clinical and genetic data from 4,567 Thai patients with cancer in the hereditary breast-ovarian cancer (HBOC) spectrum who underwent multi-gene panel testing. Six hundred and ten individuals (13.4%) had germline P/LP variants. Detection rates of germline P/LP variants in breast, ovarian, pancreatic, and prostate cancer were 13.4%, 19.8%, 14.0%, and 7.1%, respectively. Non-BRCA gene mutations accounted for 35% of patients with germline P/LP variants. ATM was the most common non-BRCA gene mutation. Four hundred and thirty-two breast cancer patients with germline P/LP variants (80.4%) met the current NCCN genetic testing criteria. The most common indication was early-onset breast cancer. Ten patients harbored double pathogenic variants in this cohort. Our result showed that significant proportion of non-BRCA P/LP variants were identified in patients with HBOC-related cancers. These data support the benefit of multi-gene panel testing for inherited cancer susceptibility in among Thai HBOC patients. Some modifications of the testing policy may be appropriate for implementation in diverse populations. (Word count: 214 words)

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“…It is more likely to arise when either of the 2 wellknown anti-oncogenes, breast cancer type 1 (BRCA1) or BRCA2, is mutated [6] . Its risk is also increased by gene mutations in checkpoint kinase 2 (CHEK2), partner and localizer of BRCA2 (PALB2), ataxia-telangiectasia mutated (ATM), RAD51C, RAD51D, BRCA1 associated ring domain 1 (BARD1), and tumor protein 53 (TP53) [7] . The overexpression of HER2 an important BC oncogene, which is detected in about 20% of BC patients, promotes cancer stem cell formation by signalling through phosphatase and tensin homolog (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin complex 1 (mTORC1) pathway [8] .…”

mentioning

confidence: 99%

Aspirin for the primary prevention of breast cancer: an unforeseen advantage

Sheikh¹,

Masood²,

Abro³

et al. 2023

International Journal of Surgery: Global Health

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

Cited by 40 publications

References 72 publications

Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA

Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA

Germline mutations in hereditary breast-ovarian cancer spectrum in Thailand: Results from multi-gene panel testing in 4,567 Thai patients

Aspirin for the primary prevention of breast cancer: an unforeseen advantage

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