Germline variants of Brazilian women with breast cancer and detection of a novel pathogenic ATM deletion in early-onset breast cancer

Bandeira, Gabriel; Rocha, Kátia Bones; Lazar, Monize; Ezquina, Suzana; Yamamoto, Guilherme Lopes; Varela, M.; Takahashi, Vanessa; Aguena, Meire; Gollop, Thomaz Rafael; Zatz, Mayana; Passos‐Bueno, Maria Rita; Krepischi, Ana Cristina Victorino; Okamoto, Oswaldo Keith

doi:10.1007/s12282-020-01165-1

Cited by 10 publications

(8 citation statements)

References 35 publications

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“…As seen in other studies, the PGVs most commonly found were in genes associated with high HBOC risk, with the overall diagnostic yield ranging from 11.1% (US Hispanic) to 20.8% (Mexico, Central America, and the Caribbean). [19][20][21][22][23][24][25][26][27][28][29][30][31][32]34,59 Although largely limited to reporting on the results from BRCA1 and BRCA2 testing, a large study demonstrated that the yield of BRCA1 and BRCA2 PGVs varies greatly by country. 36 Furthermore, the first results from the Latin American Consortium for HBOC (LACAM) have demonstrated the diversity of PGVs across many HCS genes in this population.…”

Section: Discussionmentioning

confidence: 99%

Germline Pathogenic Variant Prevalence Among Latin American and US Hispanic Individuals Undergoing Testing for Hereditary Breast and Ovarian Cancer: A Cross-Sectional Study

Gomez¹,

Achatz

Hurtado

et al. 2022

JCO Global Oncology

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PURPOSE To report on pathogenic germline variants detected among individuals undergoing genetic testing for hereditary breast and/or ovarian cancer (HBOC) from Latin America and compare them with self-reported Hispanic individuals from the United States. METHODS In this cross-sectional study, unrelated individuals with a personal/family history suggestive of HBOC who received clinician-ordered germline multigene sequencing were grouped according to the location of the ordering physician: group A, Mexico, Central America, and the Caribbean; group B, South America; and group C, United States with individuals who self-reported Hispanic ethnicity. Relatives who underwent cascade testing were analyzed separately. RESULTS Among 24,075 unrelated probands across all regions, most were female (94.9%) and reported a personal history suggestive of HBOC (range, 65.0%-80.6%); the mean age at testing was 49.1 ± 13.1 years. The average number of genes analyzed per patient was highest in group A (A 63 ± 28, B 56 ± 29, and C 40 ± 28). Between 9.1% and 18.7% of patients had pathogenic germline variants in HBOC genes (highest yield in group A), with the majority associated with high HBOC risk. Compared with US Hispanics individuals the overall yield was significantly higher in both Latin American regions (A v C P = 1.64×10–9, B v C P < 2.2×10–16). Rates of variants of uncertain significance were similar across all three regions (33.7%-42.6%). Cascade testing uptake was low in all regions (A 6.6%, B 4.5%, and C 1.9%). CONCLUSION This study highlights the importance of multigene panel testing in Latin American individuals with newly diagnosed or history of HBOC, who can benefit from medical management changes including targeted therapies, eligibility to clinical trials, risk-reducing surgeries, surveillance and prevention of secondary malignancy, and genetic counseling and subsequent cascade testing of at-risk relatives.

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Section: Discussionmentioning

confidence: 99%

Germline Pathogenic Variant Prevalence Among Latin American and US Hispanic Individuals Undergoing Testing for Hereditary Breast and Ovarian Cancer: A Cross-Sectional Study

Gomez¹,

Achatz

Hurtado

et al. 2022

JCO Global Oncology

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“…The five most recurrent variants were: BRCA1:c.5266dupC, found by other 18 studies 18, 20, 24-39 , BRCA1:c.3331_3334delCAAG, found in other 12 studies 18,20,24,27,29,31,32,34,35,37,39,40 , BRCA2:c.2808_2811delACAA found in other seven studies 18, 29-31, 34, 35, 39 , BRCA1: c.1687C>T found in six studies 26,31,32,34,35 and BRCA1:c.211A>G found in other five studies [35][36][37][38]40 . We also observed some recurrent pathogenic variants in other genes: TP53:c.1010G>A, found in four other studies 20,[38][39][40] , CHEK2:c.349A>G, found in two other studies 38,43 ; MUTYH:c.1147delC 43 Transheterozygosity, i.e. heterozygosity at two different loci 47 , is rare among patients at risk of hereditary cancers.…”

Section: Discussionmentioning

confidence: 74%

“…Among the 56 variants we detected, [35][36][37][38]40 . We also observed some recurrent pathogenic variants in other genes: TP53:c.1010G>A, found in four other studies 20,[38][39][40] , CHEK2:c.349A>G, found in two other studies 38,43 ; MUTYH:c.1147delC 43 Transheterozygosity, i.e. heterozygosity at two different loci 47 , is rare among patients at risk of hereditary cancers.…”

Section: Discussionmentioning

confidence: 95%

The genetics of hereditary cancer risk syndromes in Brazil: a comprehensive analysis of 1682 patients

Coelho

et al. 2021

Preprint

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Hereditary cancer risk syndromes are a group of disorders caused by germline variants in a growing number of genes. Most studies on hereditary cancer have been conducted in white populations. Here we report the largest study in Brazilian individuals with multiple, self-reported, ethnicities. We genotyped 1682 individuals from all regions of the country who were referred to genetic testing for hereditary cancer risk with multigene Next-generation sequencing (NGS) panels. Most were women, and had a personal and/or family history of cancer. The majority of cancer cases were breast and ovarian. We identified a total of 321 pathogenic/likely pathogenic (P/LP) variants in 305 people (18.1%), corresponding to 166 unique variants. These variants were distributed among 32 genes, and most were detected on BRCA1 and BRCA2 (129 patients, 26.2% and 14.3% of all P/LP hits, respectively). The prevalence of any genes transheterozygosity in our sample was 0.89% (15/1682). The BRCA1/BRCA2 double heterozygosity rate was 0.78% (1/129) for BRCA variants carriers and 0.06% (1/1682) overall. We classified patients according to the NCCN and Brazilian National Health Agency (ANS) genetic testing recommendation criteria. We found that the criteria had false negative rates of 17.3% and 44.2%, meaning that both failed to detect a substantial part of P/LP positive patients. Therefore, our results show that NGS adds to knowledge on the Brazilian spectrum of germline variants associated with cancer risk and indicate that Brazilian testing guidelines should be improved.

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“…The reported germline I482* variant in BRCA1 gene was associated with familial ovarian cancer predisposition in German and Japanese populations [ 20 , 21 ]. Q1756fs*74 in BRCA1 gene was also observed in Italian, Israel, USA, Brazilian, Ukrainian, Polish and Czech population with familial breast and ovarian cancer [ [22] , [23] , [24] , [25] , [26] , [27] ]. The 3rd most frequent was Q934* which had been associated with epithelial ovarian cancer in Turkish population and; familial and non-familial ovarian cancer in Japanese and Argentinian [ [28] , [29] , [30] , [31] ].…”

Section: Discussionmentioning

confidence: 92%

Germline landscape of BRCAs by 7-site collaborations as a BRCA consortium in Turkey

Bişgin¹,

Sağ²,

Doğan³

et al. 2022

The Breast

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Germline variants of Brazilian women with breast cancer and detection of a novel pathogenic ATM deletion in early-onset breast cancer

Cited by 10 publications

References 35 publications

Germline Pathogenic Variant Prevalence Among Latin American and US Hispanic Individuals Undergoing Testing for Hereditary Breast and Ovarian Cancer: A Cross-Sectional Study

Germline Pathogenic Variant Prevalence Among Latin American and US Hispanic Individuals Undergoing Testing for Hereditary Breast and Ovarian Cancer: A Cross-Sectional Study

The genetics of hereditary cancer risk syndromes in Brazil: a comprehensive analysis of 1682 patients

Germline landscape of BRCAs by 7-site collaborations as a BRCA consortium in Turkey

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