The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing Analysis

Andrikopoulou, Αngeliki; Chatzinikolaou, Spyridoula; Kyriopoulos, Ilias; Bletsa, Garyfalia; Kaparelou, Maria; Liontos, Michalis; Dimopoulos, Meletios-Athanasios; Zagouri, Flora

doi:10.3389/fonc.2021.797505

Cited by 6 publications

(14 citation statements)

References 26 publications

(44 reference statements)

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“…[14] Analysis of hormonal status indicates EOBCs in our setting more often tend to be hormone receptor (HR) negative when compared with LOBCs (47.70% vs 44.30%) contrary to the ndings of Adrikopoulou et al [4] in Greece who obtained 21.9% HR negative status among young women compared to 30.0% in the older women. [4] Intrinsic Molecular subtypes of breast cancer in the current study are dominated by TNBCs among EOBCs when compared to LOBCs (26.40% against 24.30%). TNBC is however equally the most frequent molecular subtype in both age groups.…”

Section: Years[6]contrasting

confidence: 52%

“…These ndings differ from that of studies by Andrikopoulou et al who found a similar trend but higher rates in younger patients than in older patients. [4] In sub-Saharan Africa, breast cancer has been reported to be more aggressive, and of higher grade than breast cancer diagnosed in developed countries [10].…”

Section: Years[6]mentioning

confidence: 99%

“…[3] Among premenopausal women, it has been reported that those under 40 years of age have a higher risk of dying from breast cancer. [4] Studies have linked young age to more aggressive tumour biology, poorer prognosis and worse clinical outcome. EOBC has been reported to be more commonly HER-2 enriched (22%), [3] and have lower frequency of luminal A tumours (17.2%) when compared to late onset breast cancer ( LOBC) ( 30%) in women 40 years or older.…”

Section: Introductionmentioning

confidence: 99%

“…High tumour grade, multifocal disease, and nodal involvement are some of the other histopathological characteristics that are more frequently associated with EOBC. [3,4] When compared, younger patients are diagnosed at a more advanced stage than older patients. These aggressive characteristics correlate with a poorer prognosis and a greater mortality rate (up to 1.5 times) compared to LOBC in older women.…”

Section: Introductionmentioning

confidence: 99%

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Clinicopathologic characteristics of early-onset breast cancer: A comparative analysis of cases from across Ghana

Akakpo

Imbeah²,

Edusei³

et al. 2022

Preprint

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Background: Breast cancer is the commonest cancer diagnosed globally and the second leading cause of cancer-related mortality among persons younger than 40 years. This study comparatively reviewed the demographic, pathologic and molecular features of Early-Onset Breast Cancer (EOBC) reported in Ghana in relation to Late Onset Breast Cancer (LOBC). Methods: A descriptive, cross-sectional design was used, with purposive sampling of retrospective histopathology data from 2019 to 2021. Core/incision biopsy, mastectomy and matched immunohistochemistry reports were merged into a single file and analysed with SPSS v. 20.0. Descriptive statistics of frequencies and percentages were used to describe categorical variables. Cross-tabulation and chi-square test was done at a 95% confidence interval with significance established at p<0.05Results: A total of 2,418 cases were included in the study with 20.2% (488 cases) being EOBCs and 79.8% (1,930 cases) being LOBCs. The median age at diagnosis was 34.66 (IQR: 5.55) in the EOBC group (<40 years) and 54.29 (IQR: 16.86) in the older, LOBC group (>/40 years). Invasive carcinoma - No Special Type (NST) was the commonest tumour type with grade III tumours being the highest recorded tumour grade in both age groups. Perineural invasion was statistically significant with age. EOBC was associated with higher DCIS component (24.8% vs 21.6%), lower hormone-receptor-positive status (52.30% vs 55.70%), higher proliferation index (Ki-67>20: 82.40% vs 80.30%) and a higher number of involved lymph nodes (13.80 vs 9.00%). Triple-Negative Breast cancer (26.40% vs 24.30%) was the most predominant molecular subtype of EOBC. Conclusion: EOBCs in our setting are generally more aggressive with poorer prognostic histopathological and molecular features when compared with LOBCs. A larger data set is needed to explain the lack of statistical significance of pathological features. Further molecular and genetic studies to understand the molecular genetic drivers of the general poorer outcome of EOBCs in our setting is recommended.

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Section: Years[6]contrasting

confidence: 52%

Section: Years[6]mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Clinicopathologic characteristics of early-onset breast cancer: A comparative analysis of cases from across Ghana

Akakpo

Imbeah²,

Edusei³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Signal processing, base calling, and alignment to the hg19 reference genome operated on the Torrent Suite 5.6 (Life Technologies). The reference genome was used for the comparison and it represents the normal sequence, as previously described [ 9 , 10 , 11 ]. For the downstream analyses of variant calling and data trimming alignment, the Ion Reporter 5.6 software was used.…”

Section: Methodsmentioning

confidence: 99%

Next-Generation Sequencing in Lung Cancer Patients: A Comparative Approach in NSCLC and SCLC Mutational Landscapes

Pop-Bica

Ciocan

Braicu

et al. 2022

JPM

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Background: Lung cancer remains one of the most diagnosed malignancies, being the second most diagnosed cancer, while still being the leading cause of cancer-related deaths. Late diagnosis remains a problem, alongside the high mutational burden encountered in lung cancer. Methods: We assessed the genetic profile of cancer genes in lung cancer using The Cancer Genome Atlas (TCGA) datasets for mutations and validated the results in a separate cohort of 32 lung cancer patients using tumor tissue and whole blood samples for next-generation sequencing (NGS) experiments. Another separate cohort of 32 patients was analyzed to validate some of the molecular alterations depicted in the NGS experiment. Results: In the TCGA analysis, we identified the most commonly mutated genes in each lung cancer dataset, with differences among the three histotypes analyzed. NGS analysis revealed TP53, CSF1R, PIK3CA, FLT3, ERBB4, and KDR as being the genes most frequently mutated. We validated the c.1621A>C mutation in KIT. The correlation analysis indicated negative correlation between adenocarcinoma and altered PIK3CA (r = −0.50918; p = 0.0029). TCGA survival analysis indicated that NRAS and IDH2 (LUAD), STK11 and TP53 (LUSC), and T53 (SCLC) alterations are correlated with the survival of patients. Conclusion: The study revealed differences in the mutational landscape of lung cancer histotypes.

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The CHK2 kinase is recurrently mutated and functionally impaired in the germline of pediatric cancer patients

Wagener

Walter

Auer

et al. 2022

Intl Journal of Cancer

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Predisposing CHEK2 germline variants are associated with various adult‐type malignancies, whereas their impact on cancer susceptibility in childhood cancer is unclear. To understand the frequency of germline variants in the CHEK2 gene and their impact on pediatric malignancies, we used whole‐exome sequencing to search for CHEK2 variants in the germlines of 418 children diagnosed with cancer in our clinics. Moreover, we performed functional analysis of the pathogenic CHEK2 variants to analyze the effect of the alterations on CHK2 protein function. We detected a CHEK2 germline variant in 32/418 (7.7%) pediatric cancer patients and 46.8% of them had leukemia. Functional analysis of the pathogenic variants revealed that 5 pathogenic variants impaired CHK2 protein function. 6/32 patients carried one of these clearly damaging CHEK2 variants and two of them harbored a matching family history of cancer. In conclusion, we detected germline CHEK2 variants in 7.7% of all pediatric cancer patients, of which a minority but still relevant fraction of approximately 20% had a profound impact on protein expression or its phosphorylation after irradiation‐induced DNA damage. Accordingly, we conclude that CHEK2 variants increase the risk for not only adult‐onset but also pediatric cancer.

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The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing Analysis

Cited by 6 publications

References 26 publications

Clinicopathologic characteristics of early-onset breast cancer: A comparative analysis of cases from across Ghana

Clinicopathologic characteristics of early-onset breast cancer: A comparative analysis of cases from across Ghana

Next-Generation Sequencing in Lung Cancer Patients: A Comparative Approach in NSCLC and SCLC Mutational Landscapes

The CHK2 kinase is recurrently mutated and functionally impaired in the germline of pediatric cancer patients

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