Germline APOBEC3B deletion influences clinicopathological parameters in luminal-A breast cancer: evidences from a southern Brazilian cohort

Vitiello, Glauco Akelinghton Freire; Pereira, Nathalia de Sousa; Amarante, Marla Karine; Banin-Hirata, Bruna Karina; Campos, Clodoaldo Zago; Oliveira, Karen Brajão de; Guembarovski, Roberta Losi; Watanabe, Maria Angélica Ehara

doi:10.1007/s00432-020-03208-8

Cited by 4 publications

(6 citation statements)

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“…The APOBEC3A/B germline deletion has been highlighted as a susceptibility marker for the development of BC in Asian and Caucasian populations [ 58 ], but a previous study from our research group suggests that there is no association between APOBEC3A/B genotypes and BC susceptibility in the Brazilian population [ 41 ]. Other studies show that the loss of the APOBEC3B gene can increase susceptibility to viral infection, as in infections by HIV, HBV, and HPV [ 59 , 60 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

“…For the present study, we used data from overlapping BC cohorts derived from two previous studies by our group investigating MMTV-like prevalence and APOBEC3A/B association with BC susceptibility [ 40 , 41 ]. The patients were being treated at Londrina Cancer Hospital (LCH) under the Brazilian Public Health System (SUS).…”

Section: Methodsmentioning

confidence: 99%

“…APOBEC3A/B genotyping was performed by allele-specific PCR [ 41 ], while the detection of MMTV-like env in BC tissue samples was performed using a nested PCR protocol [ 40 ]. For 35 patients, raw Sanger-sequencing data for the inner nested PCR-amplified MMTV-like env sequence were also available and chromatograms were inspected using the BioEdit7 software.…”

Section: Methodsmentioning

confidence: 99%

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Involvement of APOBEC3A/B Deletion in Mouse Mammary Tumor Virus (MMTV)-like Positive Human Breast Cancer

2023

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The association between mouse mammary tumor virus (MMTV)-like sequences and human breast cancer (BC) is largely documented in the literature, but further research is needed to determine how they influence carcinogenesis. APOBEC3 cytidine deaminases are viral restriction factors that have been implicated in cancer mutagenesis, and a germline deletion that results in the fusion of the APOBEC3A coding region with the APOBEC3B 3′-UTR has been linked to increased mutagenic potential, enhanced risk of BC development, and poor prognosis. However, little is known about factors influencing APOBEC3 family activation in cancer. Thus, we hypothesized that MMTV infection and APOBEC3-mediated mutagenesis may be linked in the pathogenesis of BC. We investigated APOBEC3A/B genotyping, MMTV-like positivity, and clinicopathological parameters of 209 BC patients. We show evidence for active APOBEC3-mediated mutagenesis in human-derived MMTV sequences and comparatively investigate the impact of APOBEC3A/B germline deletion in MMTV-like env positive and negative BC in a Brazilian cohort. In MMTV-like negative samples, APOBEC3A/B deletion was negatively correlated with tumor stage while being positively correlated with estrogen receptor expression. Although APOBEC3A/B was not associated with MMTV-like positivity, samples carrying both MMTV-like positivity and APOBEC3A/B deletion had the lowest age-at-diagnosis of all study groups, with all patients being less than 50 years old. These results indicate that APOBEC3 mutagenesis is active against MMTV-like sequences, and that APOBEC3A/B deletion might act along with the MMTV-like presence to predispose people to early-onset BC.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Involvement of APOBEC3A/B Deletion in Mouse Mammary Tumor Virus (MMTV)-like Positive Human Breast Cancer

2023

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“…This mutagenic process, while increasing genomic instability and promoting cellular transformation, shows great potential to generate neoepitopes that can be recognized by the host immune system, being associated with high immunological infiltration in tumor tissue [58]. Strikingly, a germline deletion linking APOBEC3A and APOBEC3B loci, which enhances APOBEC3A expression and APOBEC-derived mutagenesis in cancer, has been associated with higher neoepitope loads and immunologic infiltrate [58] and negatively correlated with LNM in BC [59].…”

Section: Discussionmentioning

confidence: 99%

Mouse Mammary Tumor Virus (MMTV)-Like env Sequence in Brazilian Breast Cancer Samples: Implications in Clinicopathological Parameters in Molecular Subtypes

Pereira

Vitiello

Banin-Hirata

et al. 2020

IJERPH

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Background: Breast cancer (BC) is a complex disease in which susceptibility and clinical course depend on multiple factors. Evidence suggests that a mouse mammary tumor virus (MMTV)-homolog may be present in human BCs; however, little is known about its clinical implications. Methods: MMTV-like env nucleotide-sequence was searched in tumor and tumor-adjacent tissues from 217 Brazilian BC patients through nested-PCR and confirmed through PCR-sequencing. Blood samples were also tested for patients with MMTV-like env gene-positive tumors. Correlations with clinicopathological parameters were evaluated. Results: MMTV-like env sequence was detected in tumor and tumor-adjacent tissue samples from 41/217 and 30/196 patients, respectively. In blood, MMTV-like was detected in 17/32 patients. In Luminal-B tumors, MMTV-like in tumor tissue was negatively correlated with tumor size and disease stage, whereas in HER2 tumors it anti-correlated with lymph node metastasis (LNM) and disease stage. Considering blood, MMTV-like env gene positivity negatively correlated with age in general BC, while in Luminal-A tumors it positively correlated with Ki67 but negatively correlated with age and LNM. The associations with decreased LNM frequency were independent of other prognostic factors. Conclusion: MMTV-like env positivity is associated with better prognostic parameters in BC subtypes, which might be explainable by its anti-metastatic potential and by putative activation of immune milieu.

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“…Notably, numerous tumor types have been assessed for the potential association between the APOBEC3A/B deletion variant and cancer risk. However, such studies have mainly provided contradicting results (Table S1 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ).…”

Section: Introductionmentioning

confidence: 99%

APOBEC3A/B deletion polymorphism and endometrial cancer risk

et al. 2022

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Background A common 30 kb deletion affecting the APOBEC3A and APOBEC3B genes has been linked to increased APOBEC activity and APOBEC‐related mutational signatures in human cancers. The role of this deletion as a cancer risk factor remains controversial. Materials and Methods We genotyped the APOBEC3A/B deletion in a sample of 1,470 Norwegian endometrial cancer cases and compared to 1,918 healthy controls. For assessment across Caucasian populations, we mined genotypes of the SNP rs12628403, which is in strong linkage disequilibrium with the deletion, in a GWAS dataset of 4,274 cases and 18,125 healthy controls, through the ECAC consortium. Results We found the APOBEC3A/B deletion variant to be significantly associated with reduced risk of endometrial cancer among Norwegian women (OR = 0.75; 95% CI = 0.62–0.91; p = 0.003; dominant model). Similar results were found in the subgroup of endometrioid endometrial cancer (OR = 0.64; 95% CI = 0.51–0.79; p = 3.6 × 10 −5 ; dominant model). The observed risk reduction was particularly strong among individuals in the range of 50–60 years of age (OR = 0.51; 95% CI = 0.33–0.78; p = 0.002; dominant model). In the different populations included in the ECAC dataset, the ORs varied from 0.85 to 1.05. Although five out of six populations revealed ORs <1.0, the overall estimate was nonsignificant and, as such, did not formally validate the findings in the Norwegian cohort. Conclusion The APOBEC3A/B deletion polymorphism is associated with a decreased risk of endometrial cancer in the Norwegian population.

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Germline APOBEC3B deletion influences clinicopathological parameters in luminal-A breast cancer: evidences from a southern Brazilian cohort

Cited by 4 publications

References 46 publications

Involvement of APOBEC3A/B Deletion in Mouse Mammary Tumor Virus (MMTV)-like Positive Human Breast Cancer

Involvement of APOBEC3A/B Deletion in Mouse Mammary Tumor Virus (MMTV)-like Positive Human Breast Cancer

Mouse Mammary Tumor Virus (MMTV)-Like env Sequence in Brazilian Breast Cancer Samples: Implications in Clinicopathological Parameters in Molecular Subtypes

APOBEC3A/B deletion polymorphism and endometrial cancer risk

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