scholarly journals Distinct Signatures of Genomic Copy Number Variants Define Subgroups of Merkel Cell Carcinoma Tumors

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1134
Author(s):  
Natasha T. Hill ◽  
David Kim ◽  
Klaus J. Busam ◽  
Emily Y. Chu ◽  
Clayton Green ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Copy Number ◽  
Copy Number Variants ◽  
Group Signature ◽  
Merkel Cell ◽  
Structural Variations ◽  
Structure Variation ◽  
Viral Oncogenes ◽  
Mutation Burden

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Most MCC tumors contain integrated Merkel cell polyomavirus DNA (virus-positive MCC, VP-MCC) and carry a low somatic mutation burden whereas virus-negative MCC (VN-MCC) possess numerous ultraviolet-signature mutations. In contrast to viral oncogenes and sequence mutations, little is known about genomic structural variants in MCC. To identify copy number variants in commonly altered genes, we analyzed genomic DNA from 31 tumor samples using the Nanostring nCounter copy number cancer panel. Unsupervised clustering revealed three tumor groups with distinct genomic structural variant signatures. The first cluster was characterized by multiple recurrent deletions in genes such as RB1 and WT1. The second cluster contained eight VP-MCC and displayed very few structural variations. The final cluster contained one VP-MCC and four VN-MCC with predominantly genomic amplifications in genes like MDM4, SKP2, and KIT and deletions in TP53. Overall, VN-MCC contained more structure variation than VP-MCC but did not cluster separately from VP-MCC. The observation that most MCC tumors demonstrate a deletion-dominated structural group signature, independent of virus status, suggests a shared pathophysiology among most VP-MCC and VN-MCC tumors.

scholarly journals Merkel Cell Carcinoma Patients Presenting Without a Primary Lesion Have Elevated Markers of Immunity, Higher Tumor Mutation Burden, and Improved Survival

2017 ◽  
Vol 24 (4) ◽  
pp. 963-971 ◽  
Author(s):  
Natalie Vandeven ◽  
Christopher W. Lewis ◽  
Vladimir Makarov ◽  
Nadeem Riaz ◽  
Kelly G. Paulson ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Primary Lesion ◽  
Merkel Cell ◽  
Tumor Mutation Burden ◽  
Mutation Burden

Involvement of Felis catus papillomavirus type 2 in the tumorigenesis of feline Merkel cell carcinoma

2021 ◽  
pp. 030098582110454
Author(s):  
Soma Ito ◽  
James K. Chambers ◽  
Ayumi Sumi ◽  
Nanako Yamashita-Kawanishi ◽  
Tetsuo Omachi ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Single Case ◽  
Felis Catus ◽  
Merkel Cell ◽  
Cutaneous Lesions ◽  
Viral Oncogenes ◽  
P53 Immunoreactivity

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor. We recently demonstrated that cats with MCC often have other proliferative cutaneous lesions, such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Based on this finding, we hypothesize that Felis catus papillomavirus (FcaPV) is involved in the development of MCC in cats, similar to SCC and BCC. To investigate this hypothesis, the presence of FcaPV nucleic acid and immunoreactivity for tumor suppressor proteins were examined in 21 feline MCC cases. Polymerase chain reaction using FcaPV type-specific primers detected FcaPV2 DNA in 20/21 samples of MCC. The complete FcaPV2 sequence was characterized in one case. In situ hybridization for FcaPV2 E7 revealed punctate nuclear signals within tumor cells in 19/21 MCC. Increased immunoreactivity for p16CDKN2A protein and decreased immunoreactivity for retinoblastoma (pRb) and p53 proteins were observed in 20/21 MCC. These results suggest that feline MCC cases are infected with FcaPV2 and the subsequent inhibition of pRb and p53 induced by integrated viral oncogenes is associated with feline MCC tumorigenesis, similar to other PV-induced proliferative cutaneous lesions. On the other hand, the single case of FcaPV2-negative MCC showed strong p53 immunoreactivity, suggesting mutations in p53 caused by cancer inducers other than FcaPV2 infection in this case. The present study suggests FcaPV2 as a cause of feline MCC.

Somatic mutational profile of Merkel cell carcinoma treated with immune checkpoint blockade: Preliminary results from a planned multiplatform analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21064-e21064
Author(s):  
Evan Rosenbaum ◽  
Ciara Marie Kelly ◽  
Christopher Andrew Barker ◽  
Travis Adamson ◽  
Hannah Kiesler ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Blockade ◽  
Driver Mutations ◽  
Exome Capture ◽  
Merkel Cell ◽  
Mutation Burden

e21064 Background: Merkel cell carcinoma (MCC) is an immunogenic neuroendocrine malignancy with promising responses to immune checkpoint blockade (ICB). Although ICB is standard of care in advanced MCC patients, approximately 50% of patients are resistant to ICB. Thus, it is crucial to identify biomarkers predictive of response. Methods: To understand the genomic landscape of MCC, we performed exome capture sequencing on 27 tumor and matched normal samples from 25 patients with MCC treated at Memorial Sloan Kettering. Herein, we report the analysis of 16 paired samples from 14 patients. Nonsynonymous, high-confidence somatic mutations were identified and tumor reads aligned to the Merkel cell polyoma virus (MCPyV) were quantified. Results: Tumor and matched normal samples were sequenced to a median target coverage depth of 53x and 79x reads, respectively. One sample was not analyzed due to inadequate coverage. The MCPyV genome was detected in 12 of 13 patients (92%). The median somatic mutation burden among analyzed samples was 19 nonsynonymous variants per exome (range: 8 - 120). No recurrent driver mutations were identified in any sample. Four samples lacked potential driver mutations and, among the remaining 11 samples, 36 putatively oncogenic mutations were detected in 33 genes (variant allele frequency: 0.08 – 1), including genes involved in the cell cycle checkpoint ( TP53, RB1), DNA damage repair ( ERCC4, FANCA, FANCD2), PI3K-AKT-mTOR ( PIK3CA, PIK3CG), and Notch ( NOTCH1, NOTCH2) pathways. One sample with undetected MCPyV DNA demonstrated loss of heterozygosity of both TP53 and RB1. Four samples contained strand coordinated clusters of mutations in more than 20 distinct gene regions, suggesting an APOBEC-high mutagenesis signature. Conclusions: The MCPyV genome was detected in most tumors analyzed and tumor mutation burden was low in such tumors, consistent with published literature. Analysis of an additional 11 sample pairs is ongoing, along with personalized neoantigen binding predictions on all samples. Immunohistochemistry (IHC) for PDL1 and CD8 expression is in progress. Associations between the aforementioned and response to ICB will be reported.

scholarly journals Merkel Cell Carcinoma from Molecular Pathology to Novel Therapies

2021 ◽  
Vol 22 (12) ◽  
pp. 6305
Author(s):  
Karolina Stachyra ◽  
Monika Dudzisz-Śledź ◽  
Elżbieta Bylina ◽  
Anna Szumera-Ciećkiewicz ◽  
Mateusz J. Spałek ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Surgical Excision ◽  
Lymph Node Biopsy ◽  
Merkel Cell ◽  
First Line Therapy ◽  
Mutation Burden ◽  
Node Metastases

Merkel cell carcinoma (MCC) is an uncommon and highly aggressive skin cancer. It develops mostly within chronically sun-exposed areas of the skin. MCPyV is detected in 60–80% of MCC cases as integrated within the genome and is considered a major risk factor for MCC. Viral negative MCCs have a high mutation burden with a UV damage signature. Aberrations occur in RB1, TP53, and NOTCH genes as well as in the PI3K-AKT-mTOR pathway. MCC is highly immunogenic, but MCC cells are known to evade the host’s immune response. Despite the characteristic immunohistological profile of MCC, the diagnosis is challenging, and it should be confirmed by an experienced pathologist. Sentinel lymph node biopsy is considered the most reliable staging tool to identify subclinical nodal disease. Subclinical node metastases are present in about 30–50% of patients with primary MCC. The basis of MCC treatment is surgical excision. MCC is highly radiosensitive. It becomes chemoresistant within a few months. MCC is prone to recurrence. The outcomes in patients with metastatic disease are poor, with a historical 5-year survival of 13.5%. The median progression-free survival is 3–5 months, and the median overall survival is ten months. Currently, immunotherapy has become a standard of care first-line therapy for advanced MCC.

A Case of Merkel Cell Carcinoma, Successfully Treated with Radiotherapy.

1994 ◽  
Vol 56 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Fumiyoshi ASHIZUKA ◽  
Ryoji HIROSE ◽  
Kazuhiro SHIMIZU ◽  
Yoichi TANAKA ◽  
Fumi TORIYAMA
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell
Sign in / Sign up

Export Citation Format

Share Document