X chromosome gain is related to increased androgen receptor expression in male breast cancer

Oto, Enrico Di; Biserni, Giovanni Battista; Varga, Zsuzsanna; Morandi, Luca; Cucchi, M.C.; Masetti, Riccardo; Foschini, Maria Pia

doi:10.1007/s00428-018-2377-2

Cited by 9 publications

(7 citation statements)

References 40 publications

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“…Therefore, it is plausible that all those genes show copy number gain as a consequence of X-chromosome polysomy. Indeed, results obtained by fluorescent in situ hybridization confirm that the AR gene copy number parallels the X-chromosome copy number (10,11).…”

Section: Discussionmentioning

confidence: 72%

“…AR maps to the X-chromosome (9). Previous studies performed at our institutions (10,11) demonstrated Xchromosome polysomy paralleled by AR gene copy number gain in most invasive MBC, as well as in in situ carcinoma and in cancer-associated gynecomastia.…”

Section: Introductionmentioning

confidence: 70%

“…X-chromosome polysomy can be observed in 31 to 85% of the MBC neoplastic cell population (11), being more frequent in IC-NST of higher histological grade and larger size, affecting older men (11). X-chromosome polysomy can be observed in in situ carcinoma as well as in cancer-associated gynecomastia (10), thereby suggesting to favor neoplastic transformation.…”

Section: Discussionmentioning

confidence: 99%

“…In MBC, preliminary data (10) indicated that all additional AR gene copies were hypomethylated, suggesting AR protein overexpression.…”

Section: Introductionmentioning

confidence: 99%

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Methylation Profile of X-Chromosome–Related Genes in Male Breast Cancer

et al. 2020

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Background: Androgen receptor (AR) has been described to play a prominent role in male breast cancer (MBC). It maps on chromosome X, and recent reports indicate that X-chromosome polysomy is frequent in MBC. Since the response to anti-androgen therapy may depend on AR polysomy and on its overexpression similarly to prostate cancer, the aim of the present study was to investigate the DNA methylation level of AR and its coregulators, especially those mapped on the X-chromosome, that may influence the activity of AR in MBC. Methods:The DNA methylation level of AR, MAGEA2, MAGEA11, MAGEC1, MAGEC2, FLNA, HDAC6, and UXT, mapped on the X-chromosome, was evaluated by quantitative bisulfite-NGS. Bioinformatic analysis was performed in a Galaxy Project environment using BWA-METH, MethylDackel, and Methylation Plotter tools. The study population consisted of MBC (41 cases) compared with gynecomastia (17 cases).Results: MAGEA family members, especially MAGEA2, MAGEA11, MAGEC, and UXT and HDAC6 showed hypomethylation of several CpGs, reaching statistical significance by the Kruskal-Wallis test (p < 0.01) in MBC when compared to gynecomastia. AR showed almost no methylation at all. Conclusions: Our study demonstrated for the first time that MAGEA family members mapped on the X-chromosome and coregulators of AR are hypomethylated in MBC. This may lead to their overexpression, enhancing AR activity.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

“…In MBC, preliminary data (10) indicated that all additional AR gene copies were hypomethylated, suggesting AR protein overexpression.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Methylation Profile of X-Chromosome–Related Genes in Male Breast Cancer

et al. 2020

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“…Since copy number alteration may affect tumor development through changes in gene expression, the amplification of chromosomes Xq11.1-Xq11.2 has been linked to high SPIN4 levels in glioblastoma [14]. In addition, the gain of chromosome X has been connected to neoplastic transformation, including prostate cancer [40], breast cancer [41], and renal cell carcinoma [42]. We also found that high SPIN4 expression is an unfavorable prognostic factor for renal cancer using the Human Protein Atlas database (https://www.proteinatlas.org/ENSG00000186767-SPIN4/pathology/renal+cancer, accessed on 27 July 2021).…”

Section: Discussionmentioning

confidence: 99%

High SPIN4 Expression Is Linked to Advanced Nodal Status and Inferior Prognosis in Nasopharyngeal Carcinoma Patients

Chang

Chan

Chen

et al. 2021

Life

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Nasopharyngeal carcinoma (NPC), characterized by the infiltration of lymphocytes, is a malignancy derived from the epithelium of the nasopharynx. Despite its sensitivity to radiation and chemotherapy, NPC has a high propensity for recurrence and metastasis. Although lymph node levels have been indicated as an independent prognostic factor for NPC, there has been no precise prognostic biomarker to predict clinical outcomes for NPC before advanced disease. In the present study, we surveyed differentially expressed genes in NPC via the next-generation sequencing (NGS)-based Oncomine database and identified the spindlin family member 4 (SPIN4) gene as the most relevant to advanced nodal status. We collected 124 tumor samples from NPC patients receiving biopsy, and the expression level of SPIN4 was evaluated by immunohistochemistry. The results showed that tumors with high SPIN4 expression were significantly correlated with advanced nodal status (p < 0.001) and advanced AJCC stages (p < 0.001). High SPIN4 expression in tumor samples was an unfavorable prognostic factor for all three endpoints at the univariate level: disease-specific survival (DSS), distal metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) (all p < 0.05). High SPIN4 expression remained independently prognostic of worse DMeFS (p = 0.049) at the multivariate level. Using bioinformatics analysis, we further found that high SPIN4 level may link tight junctions to cancer cell survival. Collectively, these results imply that high SPIN4 expression is linked to an aggressive clinical course, including advanced nodal status and poor survival in NPC patients, emphasizing the promising prognostic utility of SPIN4 expression.

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Pathology of the male breast

Shaaban

2019

Diagnostic Histopathology

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X chromosome gain is related to increased androgen receptor expression in male breast cancer

Cited by 9 publications

References 40 publications

Methylation Profile of X-Chromosome–Related Genes in Male Breast Cancer

Methylation Profile of X-Chromosome–Related Genes in Male Breast Cancer

High SPIN4 Expression Is Linked to Advanced Nodal Status and Inferior Prognosis in Nasopharyngeal Carcinoma Patients

Pathology of the male breast

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