Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer

Lin, Pyng-Jing; Kuo, Wang-Chuang; Huang, An; Lu, Yen Shen; Lin, Ching‐Hung; Kuo, Sung‐Hsin; Wang, Ming Yang; Liu, Chun Yu; Cheng, Fiona Tsui Fen; Yeh, Ming Hsin; Li, Huei Ying; Yang, Yi; Hsu, Ya‐Chieh; Fan, Sheng Chih; Li, Long-yuan; Yu, Sung-Liang; Chang, King‐Jen; Chen, Pei Lung; Ni, Yen‐Hsuan; Huang, Chiun Sheng

doi:10.18632/oncotarget.7027

Cited by 80 publications

(86 citation statements)

References 39 publications

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“…Mutations in the ATM gene have been described in YWBC and are considerably more frequent when there is a familial history [102][103][104][105][106][107] .…”

Section: Atmmentioning

confidence: 99%

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

Gómez-Flores-Ramos¹,

Castro-Sánchez

Peña-Curiel

et al. 2017

RIC

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Young women with breast cancer (YWBC) represent roughly 15% of breast cancer (BC) cases in Latin America and other developing regions. Breast tumors occurring at an early age are more aggressive and have an overall worse prognosis compared to breast tumors in postmenopausal women. The expression of relevant proliferation biomarkers such as endocrine receptors and human epidermal growth factor receptor 2 appears to be unique in YWBC. Moreover, histopathological, molecular, genetic, and genomic studies have shown that YWBC exhibit a higher frequency of aggressive subtypes, differential tumor gene expression, increased genetic susceptibility, and specific genomic signatures, compared to older women with BC. This article reviews the current knowledge on tumor biology and genomic signatures in YWBC.

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“…Mutations in the ATM gene have been described in YWBC and are considerably more frequent when there is a familial history [102][103][104][105][106][107] .…”

Section: Atmmentioning

confidence: 99%

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

Gómez-Flores-Ramos¹,

Castro-Sánchez

Peña-Curiel

et al. 2017

RIC

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“…13,14 Recent evidence suggests mutations in PALB2, ATM , and the genes responsible for the MRN complex, RAD50, MRE11 , and NBN , play a role in hereditary cancers. 15,16 For example, PALB2 mutation carriers have a lifetime risk of breast cancer development of approximately 50%, 17,18 and ATM mutation carriers are at higher risk for development of breast, 19,20 pancreatic, 21,22 and prostate cancers. 23,24 …”

Section: Introductionmentioning

confidence: 99%

Prevalence of Homologous Recombination–Related Gene Mutations Across Multiple Cancer Types

Heeke

Pishvaian

Lynce

et al. 2018

JCO Precision Oncology

279

223

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Purpose The prevalence of homologous recombination DNA damage repair (HR-DDR) deficiencies among all tumor lineages is not well characterized. Therapy directed toward homologous recombination DDR deficiency (HRD) is now approved in ovarian and breast cancer, and there may be additional opportunities for benefit for patients with other cancers. Comprehensive evaluations for HRD are limited in part by the lack of a uniform, cost-effective method for testing and defining HRD. Methods Molecular profiles of 52,426 tumors were reviewed to identify pathogenic mutations in the HR-DDR genes ARID1A, ATM, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CHEK1/2, FANCA/C/D2/E/F/G/L, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, or WRN. From solid tumors submitted to Caris Life Sciences, molecular profiles were generated using next-generation sequencing (NGS; average read depth, 500×). A total of 17,566 tumors were sequenced with NGS600 (n = 592 genes), and 34,860 tumors underwent hotspot Illumina MiSeq platform testing (n = 47 genes). Results Of the tumors that underwent NGS600 testing, the overall frequency of HRDDR mutations detected was 17.4%, and the most commonly mutated lineages were endometrial (34.4%; n = 1,475), biliary tract (28.9%; n = 343), bladder (23.9%; n = 201), hepatocellular (20.9%; n = 115), gastroesophageal (20.8%; n = 619), and ovarian (20.0%; n = 2,489). Least commonly mutated lineages included GI stromal (3.7%; n = 108), head and neck (6.8%; n = 206), and sarcoma (9.3%; n = 592). ARID1A was the most commonly mutated gene (7.2%), followed by BRCA2 (3.0%), BRCA1 (2.8%), ATM (1.3%), ATRX (1.3%), and CHEK2 (1.3%). Conclusions HR-DDR mutations were seen in 17.4% of tumors across 21 cancer lineages, providing a path to explore the role of HRD-directed therapies, including poly-ADP ribose polymerase inhibitors, DNA-damaging chemotherapies, and newer agents such as ATR inhibitors.

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“…Although studies have demonstrated the clinical benefit of multiple-gene sequencing for the assessment of patients with high-risk hereditary cancer [21,22], little information is currently available regarding the value of multiple-gene sequencing for the assessment of the risk of hereditary breast cancer in China. The goal of this study was to identify the variant spectrum for the clinical and genetic characterization of familial breast cancer in a Chinese population.…”

Section: Introductionmentioning

confidence: 99%

Clinical and genetic characterization of hereditary breast cancer in a Chinese population

Jian

Shao

Qin

et al. 2017

Hered Cancer Clin Pract

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Background: Breast cancer develops as a result of multiple gene mutations in combination with environmental risk factors. Causative variants in genes such as BRCA1 and/or BRCA2 have been shown to account for hereditary nature of certain breast cancers. However,other genes, such as ATM, PALB2, BRIP1, CHEK, BARD1, while lower in frequency, may also increase breast cancer risk. There are few studies examining the role of these causative variants. Our study aimed to examine the clinical and genetic characterization of hereditary breast cancer in a Chinese population. Methods: We tested a panel of 27 genes implicated in breast cancer risk in 240 participants using Next-Generation Sequencing. The prevalence of genetic causative variants was determined and the association between causative variants and clinico-pathological characteristics was analyzed. Results: Causative variant rate was 19.2% in the breast cancer (case) group and 12.5% in the high-risk group. In the case group 2.5% of patients carried BRCA1 causative variant, 7.5% BRCA2 variants, 1.7% patients had MUTYH, CHEK or PALB2 variants, and 0.8% patients carried ATM, BARD1, NBN, RAD51C or TP53 variants. In the high-risk group 5. 8% women carried MUTYH causative variants, 2.5% had causative variants in ATM, 1.7% patients had variants in BRCA2 and 0.8% in BARD1, BRIP1 or CDH1. There was no significant difference in the presence of causative variants among clinical stages of breast cancer, tumor size and lymph nodes status. However, eight of the 12 BRCA1/2 causative variants were found in the TNBC group. Conclusions: We found increased genetic causative variants in the familial breast cancer group and in high-risk women with a family history of breast cancer. However, the variant MUTYH c.892-2A > G may not be directly associated with hereditary breast carcinoma.

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Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer

Cited by 80 publications

References 39 publications

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

Prevalence of Homologous Recombination–Related Gene Mutations Across Multiple Cancer Types

Clinical and genetic characterization of hereditary breast cancer in a Chinese population

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