Non-<i>BRCA1/2</i> Variants Detected in a High-Risk Chilean Cohort With a History of Breast and/or Ovarian Cancer

Adaniel, Christina; Salinas, F. Beau; Donaire, Juan Manuel; Bravo, María Eugenia; Peralta, O; Paredes, Hernando; Aliaga, Nuvia; Sola, A. Guerrero; Neira, Paulina; Behnke, Carolina; Rodriguez, Tulio E.; Torres, Soledad; López, Francisco; Hurtado, Claudia

doi:10.1200/jgo.18.00163

Cited by 7 publications

(11 citation statements)

References 81 publications

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“…Relevant works have identified pathogenic recurrent founder mutations in Mexico, Colombia, Argentina, Brazil, Chile, Costa Rica, Cuba and Peru (29). Currently, there are few studies reporting causal pathogenic variants in a more complete set of high and moderate HBOC risk genes in the region (17)(18)(19)(20)(21), in comparison with dozens of gene panel studies performed in European and American Caucasian populations. This clearly shows the important disparity in the knowledge of the genetic diversity of this disease as compared with other populations (30).…”

Section: Discussionmentioning

confidence: 99%

“…Currently, there is a limited volume of studies of genetic susceptibility to HBOC in Latin America, and the majority of them are focused on the BRCA1/2 genes. Only a few publications have described the association of pathogenic variants in genes other than BRCA1/2 in selected HBOC cases in patients from Colombia (17), Mexico (18), Brazil (19,20), and Chile (21). Therefore, a network of collaborators and cancer specialists in LA joined common efforts to create a The Latin American consortium for HBOC-LACAM.…”

Section: Introductionmentioning

confidence: 99%

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Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach

et al. 2019

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Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ∼5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment Oliver et al. Latin American HBOC Study of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH, and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A, and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach

et al. 2019

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“…Nine founder variants identified by Alvarez et al [ 6 ] in 2017, highlighted in Table 3 , were present in 50.8% of the results of this cohort. Considering the total previously reported Chilean families [ 5 – 8 , 10 , 12 , 13 ] along with this cohort, 51.9% carried one of these variants. It’s important to note that 60 families were exclusively studied for these nine variants [ 6 , 16 ] (Supplementary Table 5).…”

Section: Resultsmentioning

confidence: 95%

“…In the literature review, from 2006 to 2023, eight studies analysed the frequency of LP/P variants in BRCA1/2 in the Chilean population with cohorts of variable size, inclusion criteria, and technology used for testing [ 5 – 8 , 12 – 14 , 16 ] ( Table 4 ). One study [ 9 ] was excluded due to variant nomenclature discrepancies, and because the P variants reported were now classified as benign or VUS.…”

Section: Resultsmentioning

confidence: 99%

Variants in BRCA1/2 in a hospital-based cohort in Chile and national literature review.

Martin,

Saffie,

Hurtado

et al. 2024

ecancer Journal

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Purpose The aim was to assess the diagnostic yield of next generation sequencing (NGS) multi-gene panels for breast and ovarian cancer in a high-complexity cancer centre in Chile. Additionally, our goal was to broaden the genotypic spectrum of BRCA variants already identified in Chilean families. Methods Retrospective analysis was conducted on the genetic test results of 722 individuals from Fundación Arturo López Pérez’s genetic counselling unit between 2016 and 2021. A comprehensive literature review encompassing articles analysing the frequency of germinal pathogenic variants in BRCA1/2 within the Chilean population was undertaken. Results 23.5% of the panels had positive results, with 60% due to pathogenic variants in the BRCA1/2 genes. Seven previously unreported variants in BRCA1 from Chilean studies were identified. One or more variants of uncertain significance were detected in 31% of the results, and 11.5% of the families in this cohort presented copy number variants (CNVs) in BRCA1/2 . 8 studies analysed the frequency of pathogenic variants in BRCA1/2 in the Chilean population between 2006 and 2023, with a frequency between 7.1% and 17.1%. 51 BRCA1 variants in 149 families have been reported in Chile and 38 BRCA2 variants in 132 families. Nine founder pathogenic variants identified by one study were present in 51.9% of the total Chilean families reported. Conclusion Our findings advocate for the integration of NGS multi-gene panel testing as a primary strategy within our population. This approach allows for the comprehensive assessment of single nucleotide variants and CNVs in BRCA1/2 , alongside other high and moderately penetrant genes associated with breast and ovarian cancer.

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“…Among individuals of AJ ancestry, most breast cancers are due to three BRCA1/2 founder mutations (BRCA1: 185delAG [c.68_69del], 5382insC [c.5266dup]; BRCA2: 6174delT [c.5946del]); while in the Mexican population the founder mutation BRCA1 ex9-12del has a high frequency. The prevalence of pathogenic variants in non-BRCA genes has not been widely investigated in the Latin American Region generally, or Mexico specifically (Cock-Rada et al, 2018;Quezada Urban et al, 2018;Adaniel et al, 2019;Oliver et al, 2019;Sandoval et al, 2021;Solano et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of genetic alterations in hereditary cancer susceptibility genes in the Ashkenazi Jewish women community of Mexico

Díaz-Velásquez¹,

Gitler²,

Antoniano³

et al. 2023

Front. Genet.

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Background: Individuals of Ashkenazi Jewish ancestry have been identified as having higher prevalence of specific pathogenic variants associated with susceptibility to specific rare and chronic diseases. In Mexico, the prevalence and composition of rare cancer predisposing germline variants in Ashkenazi Jewish individuals has not been evaluated.Aim and methods: We aimed to evaluate the prevalence of pathogenic variants by massive parallel sequencing in a panel of 143 cancer-predisposing genes in 341 women from the Ashkenazi Jewish community of Mexico, who were contacted and invited to participate in the study through the ALMA Foundation for Cancer Reconstruction. Pre- and posttest genetic counseling was given and a questionnaire on personal, gyneco-obstetric, demographic and lifestyle variables was conducted. From peripheral blood DNA, the complete coding region, and splicing sites of a panel of 143 cancer susceptibility genes, including 21 clinically relevant genes, were sequenced. The Mexican founder mutation BRCA1 ex9-12del [NC_000017.10(NM_007294):c. (825+1–826-1)_(4,589+1–4,590-1)del] was also evaluated.Results: Among study participants (mean age ±standard deviation: 47 ± 14) 15% reported a personal history of cancer (50/341). Fourteen percent of participants (48/341) were carriers of pathogenic and likely pathogenic variants distributed among seven high-risk genes (APC, CHEK2, MSH2, BMPR1A, MEN1, MLH1, and MSH6), whereas 18.2% (62/341) had variants of uncertain clinical significance in genes associated with breast and ovarian cancer susceptibility (list of genes with VUS). Pathogenic and likely pathogenic variants in 16 susceptibility genes with ambiguous or non-well-established risk association for cancer were detected in 17.6% (60/341) of participants. Sixty four percent of participants reported current alcohol consumption compared with the 39 percent prevalence of alcohol consumption in Mexican women. None of the participants carried the recurrent Ashkenazi and Mexican founder mutations in BRCA1 or BRCA2, but 2% (7/341) had pathogenic Ashkenazi Jewish founder variants in BLM.Conclusion: Our findings show a diverse pathogenic variant composition among the recruited individuals of Ashkenazi Jewish ancestry in Mexico consistent with being a high-risk population for genetic diseases, which warrants further investigation to adequately assess the burden of hereditary breast cancer in this group and implement appropriate preventative programs.

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Non-BRCA1/2 Variants Detected in a High-Risk Chilean Cohort With a History of Breast and/or Ovarian Cancer

Cited by 7 publications

References 81 publications

Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach

Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach

Variants in BRCA1/2 in a hospital-based cohort in Chile and national literature review.

Evaluation of genetic alterations in hereditary cancer susceptibility genes in the Ashkenazi Jewish women community of Mexico

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