Germline mutations of PALB2 gene in a sequential series of Chinese patients with breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1530-1530
Author(s):  
Jiaojiao Zhou ◽  
Kun Zhang ◽  
Xuan Zhu ◽  
Mei Deng ◽  
Meng Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Germline Mutation ◽  
Familial Breast Cancer ◽  
Sporadic Breast Cancer ◽  
Critical Role ◽  
Germline Mutations ◽  
Chinese Patients ◽  
Breast Cancer Patients ◽  
Loss Of Function

1530 Background: PALB2 (Partner and Localizer of BRCA2) is recently recognized as a breast cancer predisposition gene, which plays a critical role in genome maintenance via interacting with BRCA1/2 and RAD51 when DNA break. Germline loss-of-function mutations in PALB2 lead to increased breast cancer risk. Since the germline mutation frequency of PALB2 is much less than BRCA1/2, the distinct mutation spectrum of PALB2 is still obscure. Therefore, we assessed the mutational frequency, spectrum and predictors of the PALB2 gene in a sequential series of Chinese breast cancer patients from our Research DNA Bank, to verify the utility of PALB2 genetic testing in Chinese population. Methods: We examined Chinese breast cancer cases (n = 2279) who agreed to participate in research DNA banking, recruited from 1990 through 2016. To identify the mutations, complete coding sequence and intron–exon boundaries of PALB2 were screened with Next Generation Sequencing. Personal and family histories were synchronously collected for mutation identification. Results: Among the 2279 breast cancer patients, 307 patients were familial breast cancer cases and the rest 1972 patients were sporadic breast cancer cases. PALB2 mutation carriers accounted for 7.8% (n = 24) and 4.8% (n = 95) in familial and sporadic breast cancer cohort separately. In total, 31 missense, 4 nonsense, 3 frameshift, 3 splicing and 1 codon mutations of PALB2 were identified in this study. Among the pathologic variants, PALB2 c.1744C > T, c.2748+1G > A, c.2749-1G > C, c.3114-1G > A were newly identified in sporadic breast cancer, and c.3271delC newly found in familial breast cancer. Based on in silico analysis, a total of 6 potential damaging missense variants were novelly found in this study, among which the PALB2 c.3035C > T was detected in both sporadic and familial breast cancer. Conclusions: Our data presents the germline mutation status of PALB2 in Chinese patients with breast cancer, suggesting that loss-of-function germline mutations of PALB2 are important in both familial and sporadic breast cancer. Clinically, this information may be helpful in genetic counseling of breast cancer patients with PALB2 germline mutation.

Somatic and germline mutation profiles of Chinese breast cancer patients younger than 35.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 554-554
Author(s):  
Ning Liao ◽  
Guo-Chun Zhang ◽  
Xiaoqing Chen ◽  
Weikai Xiao ◽  
Jianguo Lai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Patients ◽  
Germline Mutation ◽  
Early Onset ◽  
Chinese Women ◽  
Germline Mutations ◽  
Breast Cancer Patients ◽  
Early Onset Breast Cancer ◽  
Younger Women

554 Background: Limited studies have investigated the molecular underpinnings driving breast cancer development in Chinese younger women. Based from our previous data, more Chinese women are diagnosed with early-onset breast cancer than in the West. In our study, we aim to investigate the comprehensive mutational profile of Chinese women 35 years old and younger (≤35y) diagnosed with breast cancer. Methods: Targeted sequencing was performed on surgically-removed tumor tissues and blood samples collected from 589 women diagnosed with stage I-III breast cancer of various molecular subtypes at the Guangdong Provincial People’s Hospital (GPDH) using a gene panel interrogating 520 cancer-related genes. We compared the data of 53 women aged ≤35y from our cohort to the data from 33 breast cancer patients aged ≤35y included in The Cancer Genome Atlas (TCGA) dataset. Results: Among the women aged ≤35y with early-stage breast cancer from both cohorts, our cohort had more number of hormone receptor-positive (HR+) patients (GPDH, 72% vs. TCGA, 61%, P< 0.001). Analysis revealed an overall mutation detection rate of 98% in our cohort, with mutations affecting genes involved in the PI3K pathway (47%) and cell cycle pathway (23%). TP53 and PIK3CA were the most commonly mutated genes, with mutation rates of 51% and 25% from our cohort. No statistical difference in mutation profile was found between GPDH and TCGA cohorts. Moreover, germline mutations considered as pathogenic and likely pathogenic (P/LP) in breast cancer susceptibility genes including BRCA1 (n = 4), BRCA2 (n = 2), PALB2 (n = 1), PMS2 (n = 1), PTEN (n = 1), and ATM (n = 1) were detected from 18.9% (10/53) of the patients from our cohort. Women aged ≤35y had significantly more germline BRCA1 mutations than patients > 35y from our cohort (7.5%, 4/53 vs. 2.1%, 11/536 P= 0.049). Conclusions: Our study has identified the involvement of PI3K and cell cycle as the two key pathways in the early development of breast tumors in younger women. In addition, our results also support the role of P/LP germline mutations in breast oncogenesis in Chinese patients with early-onset breast cancer, indicating the need to include a more comprehensive germline mutation screening in our population.

scholarly journals BRCA1 germline mutations dominate familial breast cancer patients in Henan China

2017 ◽  
Vol 9 (12) ◽  
pp. 5295-5299 ◽  
Author(s):  
Lina Wang ◽  
Shiyuan Zhou ◽  
Jiansheng Xie ◽  
Huafang Gao ◽  
Fengyu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Familial Breast Cancer ◽  
Germline Mutations ◽  
Breast Cancer Patients

scholarly journals Mutation screening of germline TP53 mutations in high-risk Chinese breast cancer patients

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ava Kwong ◽  
Vivian Yvonne Shin ◽  
Cecilia Y. S. Ho ◽  
Chun Hang Au ◽  
Thomas P. Slavin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Germline Mutation ◽  
Early Onset ◽  
Mutation Screening ◽  
Germline Mutations ◽  
Breast Cancer Patients ◽  
History Of ◽  
History Of Cancer

Abstract Background Germline TP53 mutations are associated with Li-Fraumeni syndrome, a severe and rare hereditary cancer syndrome. Despite the rarity of germline TP53 mutations, the clinical implication for mutation carriers and their families is significant. The risk management of TP53 germline mutation carriers is more stringent than BRCA carriers, and radiotherapy should be avoided when possible. Methods TP53 gene mutation screening was performed in 2538 Chinese breast cancer patients who tested negative for BRCA mutations. Results Twenty TP53 mutations were identified with high next-generation sequencing concerning for germline mutations in Chinese breast cancer families. The majorities of the TP53 carriers had early-onset, hormone receptor-positive breast cancer, and had strong family history of cancer. Among all, 11 patients carried a germline mutation and 6 of which were likely de novo germline mutations. In addition, 1 case was suspected to be induced by chemotherapy or radiation, as this patient had no significant family history of cancer and aberrant clonal expansion can commonly include TP53 mutations. Furthermore, we have identified one mosaic LFS case. Two novel mutations (c.524_547dup and c.529_546del) were identified in patients with early-onset. Conclusions In view of the high lifetime risk of malignancy, identification of patients with germline TP53 mutations are important for clinicians to aid in accurate risk assessment and offer surveillance for patients and their families.

scholarly journals Novel Germline Mutations of BRCA1 and BRCA2 in Korean Familial Breast Cancer Patients

2019 ◽  
Vol 55 (2) ◽  
pp. 99
Author(s):  
Hee Nam Kim ◽  
Min-Ho Shin ◽  
Ran Lee ◽  
Min-Ho Park ◽  
Sun-Seog Kweon
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Familial Breast Cancer ◽  
Germline Mutations ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2

Survival in Hereditary Breast Cancer Associated With Germline Mutations of BRCA2

1999 ◽  
Vol 17 (11) ◽  
pp. 3396-3402 ◽  
Author(s):  
L. C. Verhoog ◽  
C.T.M. Brekelmans ◽  
C. Seynaeve ◽  
G. Dahmen ◽  
A. N. van Geel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Hereditary Breast Cancer ◽  
Sporadic Breast Cancer ◽  
Steroid Receptor ◽  
Germline Mutations ◽  
Breast Cancer Patients ◽  
Sporadic Cases ◽  
Disease Free

PURPOSE: Breast cancer in BRCA1 and BRCA2 gene-mutation carriers may differ from so-called sporadic breast cancer in clinical features and behavior. These potential differences may be of importance for the prevention, screening, and, ultimately, treatment of breast cancer in women with such germline mutations. Thus far, there have been very few studies on the survival of BRCA2-associated breast cancer patients. PATIENTS AND METHODS: We determined the disease-free and overall survival of 28 breast cancer patients from 14 consecutive families with eight different BRCA2 germline mutations. These patients' survival and tumor characteristics were compared with those of a control group of 112 sporadic breast cancer patients matched to them by age and year of diagnosis. RESULTS: The 5-year disease-free survival was 52% for each group (P = .91); the overall survival was 74% for BRCA2 carriers and 75% for sporadic cases (P = .50). At the time of diagnosis, tumors from the BRCA2 carriers were borderline significantly larger in comparison to the tumors in sporadic cases (P = .05), but axillary nodal status was not significantly different in the two groups (node-negativity, 63% v 52.8%, respectively; P = .34). With respect to steroid receptor status, BRCA2-associated tumors were more likely to be steroid receptor-positive, especially regarding progesterone receptor status (100% v 76.7% positive, respectively; P = .06). Stage-adjusted recurrence and death rates were nonsignificantly better for BRCA2 cases (hazard ratios of 0.84 and 0.59 [P = .61 and P = .19], respectively). In contrast, after 5 years, the rate of metachronous contralateral breast cancer in BRCA2 patients was 12% (v 2% in controls; P = .02). CONCLUSION: Patients with hereditary breast cancer due to BRCA2 have a similar prognosis when compared with age-matched sporadic breast cancer patients. Contrary to our previous observation regarding BRCA1-associated breast cancer, BRCA2 tumors tended to be steroid receptor-positive, instead of steroid receptor-negative.

scholarly journals Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Muhammad Usman Rashid ◽  
Noor Muhammad ◽  
Faiz Ali Khan ◽  
Umara Shehzad ◽  
Humaira Naeemi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Onset ◽  
Familial Breast Cancer ◽  
High Performance ◽  
Breast Cancer Patients ◽  
Germline Variants ◽  
Variants Of Unknown Significance ◽  
Breast Cancer Predisposition ◽  
Novel Variants

Abstract Background The RecQ Like Helicase (RECQL) gene has previously been shown to predispose to breast cancer mainly in European populations, in particular to estrogen receptor (ER) and/or progesterone receptor (PR) positive tumor. Here, we investigated the contribution of pathogenic RECQL germline variants to hereditary breast cancer in early-onset and familial breast cancer patients from Pakistan. Methods Comprehensive RECQL variant analysis was performed in 302 BRCA1 and BRCA2 negative patients with ER and/or PR positive breast tumors using denaturing high-performance liquid chromatography followed by DNA sequencing. Novel variants were classified using Sherloc guidelines. Results One novel pathogenic protein-truncating variant (p.W75*) was identified in a 37-year-old familial breast cancer patient. The pathogenic variant frequencies were 0.3% (1/302) in early-onset and familial breast cancer patients and 0.8% (1/133) in familial patients. Further, three novel variants of unknown significance, p.I141F, p.S182S, and p.C475C, were identified in familial breast cancer patients at the age of 47, 68, and 47 respectively. All variants were absent in 250 controls. Conclusions Our data suggest that the RECQL gene plays a negligible role in breast cancer predisposition in Pakistan.

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