Evaluation of p16 protein expression and CDKN2A deletion in conventional and fibrosarcomatous dermatofibrosarcoma protuberans

Siref, Andrew; Patel, Vatsal; Reith, John D.; Balzer, Bonnie; Shon, Wonwoo

doi:10.1016/j.pathol.2017.11.096

Cited by 3 publications

(4 citation statements)

References 2 publications

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“…Pharmacodynamics analyses also showed that the p16/ cyclin D-CDK4 pathway was associated with tumor response. In DFSP, the deletion of CDKN2A and the resulting loss of P16 expression was identified in a significant proportion of DFSPs, including fibrosarcomatous DFSP, and was shown to contribute to the progression of DFSP (Eilers et al, 2015;Siref et al, 2018;Stacchiotti et al, 2016a). Although the number of samples was low, our results were consistent with the p16 loss found in one patient without clinical benefit from pazopanib and the remaining expression in three patients with a response.…”

Section: Discussionsupporting

confidence: 85%

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A Multicenter Phase II Study of Pazopanib in Patients with Unresectable Dermatofibrosarcoma Protuberans

Delyon

Porcher

Battistella

et al. 2021

Journal of Investigative Dermatology

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Section: Discussionsupporting

confidence: 85%

“…We studied the role of the p16/cyclin D-CDK4 pathway in tumors because this pathway is known to be involved in DFSP progression (Eilers et al, 2015;Park et al, 2018;Siref et al, 2018;Stacchiotti et al, 2016a). We focused on the expression of cell-cycle regulators in the tumor samples.…”

Section: Cell-cycle Analysis and Response To Pazopanibmentioning

confidence: 99%

A Multicenter Phase II Study of Pazopanib in Patients with Unresectable Dermatofibrosarcoma Protuberans

Delyon

Porcher

Battistella

et al. 2021

Journal of Investigative Dermatology

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“…We found CDKN2A to be the most frequently altered genes detected in the relapsed patients. Indeed, CDKN2A status was found to be associated with various cancers [ 35 – 40 ]. A recent study identified CDKN2A as a tumor suppressor whose inactivation promoted homotypic cell-in-cell formation in human cancer cells [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

et al. 2018

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PurposeThe identification of genomic alterations related to recurrence in early-stage non-small cell lung cancer (NSCLC) patients may help better stratify high-risk individuals and guide treatment strategies. This study aimed to identify the molecular biomarkers of recurrence in early-stage NSCLC.ResultsOf the 42 tumors evaluable for genomic alterations, TP53 and EGFR were the most frequent alterations with population frequency 52.4% and 50.0%, respectively. Fusion genes were detected in four patients, which had lower mutational burden and relatively better genomic stability. EGFR mutation and fusion gene were mutually exclusive in this study. CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were only observed in the relapsed patients. Increased copy number alteration index was observed in early relapsed patients. Among these genomic alterations, early-stage NSCLCs harboring CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were found to be significantly associated with recurrence. Some of these new findings were validated using The Cancer Genome Atlas (TCGA) dataset.ConclusionsThe genomic alterations of CDKN2A, FAS, SUFU and SMARCA4 in early-stage NSCLC are found to be associated with recurrence, but confirmation in a larger independent cohort is required to define the clinical impact.Materials and MethodsPaired primary tumor and normal lung tissue samples were collected for targeted next-generation sequencing analysis. A panel targets exons for 440 genes was used to assess the mutational and copy number status of selected genes in three clinically relevant groups of stage I/II NSCLC patients: 1) Early relapse; 2) Late relapse; and 3) No relapse.

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“…Preserved p16 expression: The p16/cyclin D-CDK4 pathway is known to play a role in DFSP pathogenesis (Park et al, 2018). Furthermore, loss of p16 expression is associated with DFSP progression and poor prognosis (Siref et al, 2018). Whereas there was no significant difference in CDKN2A (coding for p16) expression between responders and nonresponders, Delyon et al ( 2020) observed loss of p16 expression on immunohistochemistry in one nonresponder and preserved expression in three responders.…”

Section: Discussion Of Incorrect Answersmentioning

confidence: 99%

Cells to Surgery Quiz: January 2021

Schlessinger

Erickson

2021

Journal of Investigative Dermatology

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Which of the following is true regarding trial design and outcomes in the study by Delyon et al. (2020)? a. Partial response was defined as a reduction of the largest diameter of the tumor by 50% at 12 months or at surgery, if performed before 12 months.b. The majority of patients with surgery eventually had complete resection with free margins.c. The most common cutaneous adverse effect was alopecia.d. In matched tumor samples at a 6-month status after treatment with pazopanib, VEGF receptor (VEGFR) mRNA VEGFR-2 expression was significantly greater in responders than in nonresponders.e. Participants were excluded if they had previously received imatinib or if their DFSP exhibited fibrosarcomatous transformation. 3. What finding was DFSP associated with in the phase II clinical trial Delyon et al. (2020) a. Elevated plasma levels of soluble VEGFR-2 b. Presence of the COL1A1-PDGFB fusion gene c. Preserved p16 expression d. Overexpression of the transcripts associated with the EFGR pathway e. Reduced PDGF receptor signaling See the following pages for detailed answers

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Evaluation of p16 protein expression and CDKN2A deletion in conventional and fibrosarcomatous dermatofibrosarcoma protuberans

Cited by 3 publications

References 2 publications

A Multicenter Phase II Study of Pazopanib in Patients with Unresectable Dermatofibrosarcoma Protuberans

A Multicenter Phase II Study of Pazopanib in Patients with Unresectable Dermatofibrosarcoma Protuberans

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

Cells to Surgery Quiz: January 2021

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