Epigenetic alterations in metastatic cutaneous carcinoma

Darr, Owen A.; Colacino, Justin A.; Tang, Alice; McHugh, Jonathan B.; Bellile, Emily L.; Bradford, Carol R.; Prince, Mark P.; Chepeha, Douglas B.; Rozek, Laura S.; Moyer, Jeffrey S.

doi:10.1002/hed.23701

Cited by 35 publications

(28 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This gene localizes in the X-chromosome and has been previously described as highly and specifically expressed in testis [29]. MYCL2 shows high homology with the tumor suppressor genes MYCL1 and MYC and has been found methylated in non-metastatic basal cell carcinoma, but unmethylated in metastasic basal cell carcinoma, suggesting that MYCL2 methylation status could be used as biomarker of metastasic potential [30]. …”

Section: Discussionmentioning

confidence: 99%

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

Angulo

López

Dorado³

et al. 2016

Urol Int

View full text Add to dashboard Cite

Purpose: Detection of DNA hypermethylation is emerging as a novel molecular biomarker for different malignancies. We intend to define whether a hypermethylation profile of patients with prostate cancer (PCa) predicts biochemical recurrence (BCR) after radical prostatectomy (RP). Material and Methods: Genome-wide methylation analysis was performed using the GoldenGate Methylation Cancer Panel-I (Illumina, Inc.) on 10 normal prostate tissues and 58 tumor samples from patients treated by RP followed for prostate-specific antigen (PSA) failure (>0.4 ng/ml) and disease progression. Patients were classified on the basis of D'Amico criteria according to clinical staging, PSA at diagnosis and Gleason score after pathologist review. Hypermethylation status of 1505 CpGs present in the promoter region of 807 genes was studied. Hierarchical clustering analysis was performed and relationships with outcome were investigated using log-rank analysis and Cox regression model. Results: We found 28 genes significantly hypermethylated in >20% of the tumors analyzed. Four clusters of patients were characterized by their DNA methylation profile, one at higher risk to develop BCR (p = 0.005). Multivariate analysis revealed patients in this cluster (HR 2.56), and high-risk patients (HR 4.34) according to D'Amico classification were independent predictors of BCR after prostatectomy. From the selected genes MT1A, ALOX12, GSTM2, APC, MYCL2 and RARB hypermethylation predicted BCR and GSTM2 (HR 3.78) and MYCL2 hypermethylation (HR 2.71) did so independently. Conclusion: Epigenetic silencing of GSTM2 and MYCL2 comprise novel molecular markers to predict BCR after surgery for medium- and high-risk localized PCa undergoing surgical treatment and hypermethylation of these genes could be incorporated to the clinical and pathological factors defining the patient at higher risk of PSA failure after prostatectomy. The limitation of the study is that no independent validation cohort is analysed.

show abstract

Section: Discussionmentioning

confidence: 99%

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

Angulo

López

Dorado³

et al. 2016

Urol Int

View full text Add to dashboard Cite

show abstract

“…Epigenetic changes reflect alterations in the histone supports of the nucleic acids. A recent report identified methylation profile differences in key CpG promoter sites between metastatic and nonmetastatic SCC and BCC . DNA extraction and methylation analysis using formalin‐fixed paraffin‐embedded specimens of 37 primary cutaneous SCCs (and 5 BCCs) showed hypermethylation at CpG sites and, thus, silencing of FRZB , TFAP2C , and ASCL2 in cutaneous SCC that developed metastases as opposed to the cutaneous SCC that did not.…”

Section: Introductionmentioning

confidence: 96%

Reviewing the genetic alterations in high‐risk cutaneous squamous cell carcinoma: A search for prognostic markers and therapeutic targets

et al. 2017

View full text Add to dashboard Cite

Cutaneous squamous cell carcinoma (SCC) is second only in incidence to basal cell carcinoma (BCC), effecting up to 500 000 people in the United States annually. Metastasis to regional lymph nodes occurs in approximately 5% of cases and imparts significant morbidity. Standard treatment in this group involves a combination of surgery and adjuvant radiation. Currently, there are no clinically useful biomarkers of metastatic potential in primary cutaneous SCC and histological predictors can be unreliable. The high level of mutational burden in normal UV-exposed skin has hampered the search for novel drivers of invasive disease, and indeed metastatic potential. This review outlines the clinical problems in high-risk and metastatic cutaneous SCCs, reviews the known genetic events and molecular mechanisms in high-risk primary cutaneous SCC and metastasis, and identifies avenues for further investigation and potential therapy.

show abstract

“…Although both BCCs and SCCs arise from the epidermal basal layer, they have different characteristics [5]. Though BCCs exhibit slow growth and rarely metastasize, their SCCs counterparts metastasize 2 to 5 of the time and carry a poor prognosis if metastasis has occurred [6]. Melanoma, which accounts for only 4 percent of all skin cancers, is a potentially life-threatening skin cancer due to its propensity to metastasize.…”

Section: Introductionmentioning

confidence: 99%

Phytochemicals for the Management of Melanoma

Pal¹,

Hunt²,

Diamond³

et al. 2016

MRMC

View full text Add to dashboard Cite

Melanoma claims approximately 80% of skin cancer-related deaths. Its life-threatening nature is primarily due to a propensity to metastasize. The prognosis for melanoma patients with distal metastasis is bleak, with median survival of six months even with the latest available treatments. The most commonly mutated oncogenes in melanoma are BRAF and NRAS accounting approximately 60% and 20% of cases, respectively. In malignant melanoma, accumulating evidence suggests that multiple signaling pathways are constitutively activated and play an important role in cell proliferation, cell survival, epithelial to mesenchymal transition, metastasis and resistance to therapeutic regimens. Phytochemicals are gaining considerable attention because of their low toxicity, low cost, and public acceptance as dietary supplements. Cell culture and animals studies have elucidated several cellular and molecular mechanisms by which phytochemicals act in the prevention and treatment of metastatic melanoma. Several promising phytochemicals, such as, fisetin, epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3-carbinol, and luteolin are gaining considerable attention and found in a variety of fresh fruits, vegetables, roots, and herbs. In this review, we will discuss the preventive potential, therapeutic effects, bioavailability and structure activity relationship of these selected phytochemicals for the management of melanoma.

show abstract

Epigenetic alterations in metastatic cutaneous carcinoma

Cited by 35 publications

References 48 publications

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

Reviewing the genetic alterations in high‐risk cutaneous squamous cell carcinoma: A search for prognostic markers and therapeutic targets

Phytochemicals for the Management of Melanoma

Contact Info

Product

Resources

About