TP53 germline mutations in young females with early onset breast cancer in a Mexican population.

Abstract Background To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco. Methods Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform. Results Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer. Conclusion Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.

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Familial Risks, Early-Onset Breast Cancer, and BRCA1 and BRCA2 Germline Mutations

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/95.6.448 ◽

2003 ◽

Vol 95 (6) ◽

pp. 448-457 ◽

Cited By ~ 120

Author(s):

G. S. Dite ◽

M. A. Jenkins ◽

M. C. Southey ◽

J. S. Hocking ◽

G. G. Giles ◽

...

Keyword(s):

Breast Cancer ◽

Early Onset ◽

Germline Mutations ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2

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Abstract P2-02-04: Li-Fraumeni syndrome in females with early onset breast cancer in a Mexican population

10.1158/1538-7445.sabcs16-p2-02-04 ◽

2017 ◽

Author(s):

LN Gallardo-Alvarado ◽

DF Cantu-De Leon ◽

T Tusie-Luna ◽

I Tusie-Luna ◽

J Diaz-Chavez ◽

...

Keyword(s):

Breast Cancer ◽

Early Onset ◽

Mexican Population ◽

Early Onset Breast Cancer ◽

Li Fraumeni Syndrome ◽

Li Fraumeni

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BRCA1 and BRCA2 Germline Mutations in Malaysian Women with Early-Onset Breast Cancer without a Family History

PLoS ONE ◽

10.1371/journal.pone.0002024 ◽

2008 ◽

Vol 3 (4) ◽

pp. e2024 ◽

Cited By ~ 34

Author(s):

Gaik Theng Toh ◽

Peter Kang ◽

Sharlene S. W. Lee ◽

Daphne Shin-Chi Lee ◽

Sheau Yee Lee ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Early Onset ◽

Germline Mutations ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Malaysian Women

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BRCA1 germline mutations and tumor characteristics in Chinese women with familial or early-onset breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-008-0066-6 ◽

2008 ◽

Vol 117 (1) ◽

pp. 55-60 ◽

Cited By ~ 25

Author(s):

Weiqiu Chen ◽

Kaifeng Pan ◽

Tao Ouyang ◽

Jinfeng Li ◽

Tianfeng Wang ◽

...

Keyword(s):

Breast Cancer ◽

Early Onset ◽

Chinese Women ◽

Germline Mutations ◽

Tumor Characteristics ◽

Early Onset Breast Cancer

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ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer

Salud Pública de México ◽

10.21149/spm.v56i2.7336 ◽

2014 ◽

Vol 56 (2) ◽

pp. 206 ◽

Cited By ~ 6

Author(s):

Fabiola Del Carmen Calderón-Zúñiga ◽

Guadalupe Ocampo-Gómez ◽

Francisco Carlos López-Márquez ◽

Rogelio Recio-Vega ◽

Luis Benjamín Serrano-Gallardo ◽

...

Keyword(s):

Breast Cancer ◽

Early Onset ◽

Mexican Population ◽

Mexican Women ◽

Healthy Controls ◽

Test Results ◽

Early Onset Breast Cancer ◽

Pcr Rflp ◽

Chilean Population ◽

Mexican Populations

Objective. To assess whether in Mexican population the frequencies of ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in breast cancer (BC) cases and healthy controls were different from those found in other countries. Materials and methods. Frequencies of polymorphisms conferring BC risk IVS24-9delT, IVS38-8T>C, and 5557G>A were analyzed by PCR-RFLP in 94 patients with familial and/or early onset BC, and 97 healthy controls randomly selected. Allele frequencies analysis was done using χ2 and Hardy-Weinberg test. Results. Frequencies of heterozygous were: for 5557G>A, 13% cases, 0%controls (p=0.0009); for IVS24-9delT, 21% cases, 8% controls (p=0.0122); for IVS38-8T>C, only one case. 5557G>A and IVS24-9delT were more frequent in cases than in controls. The allelic frequencies found in 5557G>A are similar to those described by González-Hormazábal in Chile. Conclusion. The similarity of results in this polymorphism between Chilean and Mexican populations may be due to both being crossbred with an Amerindian-Spanish component, while differences may be due to fact that Chilean population has a greater European component than Mexican’s.

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

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.554 ◽

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.

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