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Merkel Cell Carcinoma with a Suppressor of Fused (SUFU) Mutation: Case Report and Potential Therapeutic Implications.

Cohen PR, Kurzrock R - Dermatol Ther (Heidelb) (2015)

Bottom Line: Of interest, arsenic trioxide or bromo and extra C-terminal inhibitors impact signals downstream to SUFU, making this aberration conceivably druggable.The pathogenesis of Merkel cell carcinoma is multifactorial, and related to ultraviolet radiation exposure, immunosuppression, and Merkel cell polyomavirus.We report a patient with a mutation in SUFU, a potentially actionable component of the Hh signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of California San Diego, San Diego, CA, USA, mitehead@gmail.com.

ABSTRACT

Introduction: Merkel cell carcinoma is a neuroendocrine malignancy. Suppressor of fused (SUFU) is a tumor suppressor oncogene that participates in the Hedgehog (Hh) signaling pathway. The aim of the study was to describe a patient whose Merkel cell carcinoma demonstrated a SUFU genomic alteration.

Case study: The Hh signaling pathway is involved in the pathogenesis of several tumors, including nevoid basal cell carcinoma syndrome that is associated with an alteration of the patched-1 (PTCH1) gene. Targeted molecular therapy against smoothened (SMO) with vismodegib has been shown to be an effective therapeutic intervention for patients with PTCH-1 mutation. The reported patient was presented with metastatic Merkel cell carcinoma. Analysis of his tumor, using a next-generation sequencing-based assay, demonstrated a genomic aberration of SUFU protein, a component of the Hh signaling pathway that acts downstream to SMO and, therefore, is unlikely to be responsive to vismodegib. Of interest, arsenic trioxide or bromo and extra C-terminal inhibitors impact signals downstream to SUFU, making this aberration conceivably druggable. His tumor has initially been managed with chemotherapy (carboplatin and etoposide) and subsequent radiation therapy is planned.

Conclusion: The pathogenesis of Merkel cell carcinoma is multifactorial, and related to ultraviolet radiation exposure, immunosuppression, and Merkel cell polyomavirus. We report a patient with a mutation in SUFU, a potentially actionable component of the Hh signaling pathway.

No MeSH data available.


Related in: MedlinePlus

Tumor is present at the base of the punch biopsy specimen. It is in the deep dermis and extends into the subcutaneous tissue [hematoxylin and eosin, ×2]
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Fig3: Tumor is present at the base of the punch biopsy specimen. It is in the deep dermis and extends into the subcutaneous tissue [hematoxylin and eosin, ×2]

Mentions: Microscopic examination of the skin biopsy specimen showed an infiltrate of small blue cells with minimal cytoplasm in the deep portion of the punch biopsy and all the pieces of subcutaneous tissue (Fig. 3). The basophilic cells were uniform in size with a vesicular nucleus and small nucleoli. Numerous mitoses were appreciated and there were large areas of necrosis. The tumor invaded fascia in the deeper specimens and focally grew in close approximation to multiple blood vessels; however, no intravascular or perineural invasion was identified (Fig. 4).Fig. 3


Merkel Cell Carcinoma with a Suppressor of Fused (SUFU) Mutation: Case Report and Potential Therapeutic Implications.

Cohen PR, Kurzrock R - Dermatol Ther (Heidelb) (2015)

Tumor is present at the base of the punch biopsy specimen. It is in the deep dermis and extends into the subcutaneous tissue [hematoxylin and eosin, ×2]
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4470960&req=5

Fig3: Tumor is present at the base of the punch biopsy specimen. It is in the deep dermis and extends into the subcutaneous tissue [hematoxylin and eosin, ×2]
Mentions: Microscopic examination of the skin biopsy specimen showed an infiltrate of small blue cells with minimal cytoplasm in the deep portion of the punch biopsy and all the pieces of subcutaneous tissue (Fig. 3). The basophilic cells were uniform in size with a vesicular nucleus and small nucleoli. Numerous mitoses were appreciated and there were large areas of necrosis. The tumor invaded fascia in the deeper specimens and focally grew in close approximation to multiple blood vessels; however, no intravascular or perineural invasion was identified (Fig. 4).Fig. 3

Bottom Line: Of interest, arsenic trioxide or bromo and extra C-terminal inhibitors impact signals downstream to SUFU, making this aberration conceivably druggable.The pathogenesis of Merkel cell carcinoma is multifactorial, and related to ultraviolet radiation exposure, immunosuppression, and Merkel cell polyomavirus.We report a patient with a mutation in SUFU, a potentially actionable component of the Hh signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of California San Diego, San Diego, CA, USA, mitehead@gmail.com.

ABSTRACT

Introduction: Merkel cell carcinoma is a neuroendocrine malignancy. Suppressor of fused (SUFU) is a tumor suppressor oncogene that participates in the Hedgehog (Hh) signaling pathway. The aim of the study was to describe a patient whose Merkel cell carcinoma demonstrated a SUFU genomic alteration.

Case study: The Hh signaling pathway is involved in the pathogenesis of several tumors, including nevoid basal cell carcinoma syndrome that is associated with an alteration of the patched-1 (PTCH1) gene. Targeted molecular therapy against smoothened (SMO) with vismodegib has been shown to be an effective therapeutic intervention for patients with PTCH-1 mutation. The reported patient was presented with metastatic Merkel cell carcinoma. Analysis of his tumor, using a next-generation sequencing-based assay, demonstrated a genomic aberration of SUFU protein, a component of the Hh signaling pathway that acts downstream to SMO and, therefore, is unlikely to be responsive to vismodegib. Of interest, arsenic trioxide or bromo and extra C-terminal inhibitors impact signals downstream to SUFU, making this aberration conceivably druggable. His tumor has initially been managed with chemotherapy (carboplatin and etoposide) and subsequent radiation therapy is planned.

Conclusion: The pathogenesis of Merkel cell carcinoma is multifactorial, and related to ultraviolet radiation exposure, immunosuppression, and Merkel cell polyomavirus. We report a patient with a mutation in SUFU, a potentially actionable component of the Hh signaling pathway.

No MeSH data available.


Related in: MedlinePlus