Viral and Genomic Drivers of Squamous Cell Neoplasms Arising in the Lacrimal Drainage System
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Viral and Genomic Drivers of Squamous Cell Neoplasms Arising in the Lacrimal Drainage System. / Ramberg, Ingvild; Vieira, Filipe Garrett; Toft, Peter Bjerre; Buchwald, Christian von; Heegaard, Steffen.
In: Cancers, Vol. 14, No. 10, 2558, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Viral and Genomic Drivers of Squamous Cell Neoplasms Arising in the Lacrimal Drainage System
AU - Ramberg, Ingvild
AU - Vieira, Filipe Garrett
AU - Toft, Peter Bjerre
AU - Buchwald, Christian von
AU - Heegaard, Steffen
N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022
Y1 - 2022
N2 - The pathogenesis of squamous cell neoplasms arising in the lacrimal drainage system is poorly understood, and the underlying genomic drivers for disease development remain unexplored. We aimed to investigate the genomic aberrations in carcinomas arising in the LDS and correlate the findings to human papillomavirus (HPV) status. The HPV analysis was performed using HPV DNA PCR, HPV E6/E7 mRNA in-situ hybridization, and p16 immunohistochemistry. The genomic characterization was performed by targeted DNA sequencing of 523 cancer-relevant genes. Patients with LDS papilloma (n = 17) and LDS carcinoma (n = 15) were included. There was a male predominance (68%) and a median age at diagnosis of 46.0 years (range 27.5–65.5 years) in patients with papilloma and 63.8 years (range 34.0–87.2 years) in patients with carcinoma. Transcriptional activity of the HPV E6/E7 oncogenes was detected in the whole tumor thickness in 12/15 (80%) papillomas (HPV6, 11, 16) and 10/15 (67%) squamous cell carcinomas (SCC) (HPV11: 3/15 (20%) and HPV16: 7/15 (47%)). Pathogenic variants in PIK3CA, FGFR3, AKT1, and PIK3R1, wildtype TP53, p16 overexpression, and deregulated high-risk E6/E7 transcription characterized the HPV16-positive SCC. The deregulated pattern of HPV E6/E7 expression, correlating with HPV DNA presence and p16 positivity, supports a causal role of HPV in a subset of LDS papillomas and carcinomas. The viral and molecular profile of LDS SCC resembles that of other HPV-driven SCC.
AB - The pathogenesis of squamous cell neoplasms arising in the lacrimal drainage system is poorly understood, and the underlying genomic drivers for disease development remain unexplored. We aimed to investigate the genomic aberrations in carcinomas arising in the LDS and correlate the findings to human papillomavirus (HPV) status. The HPV analysis was performed using HPV DNA PCR, HPV E6/E7 mRNA in-situ hybridization, and p16 immunohistochemistry. The genomic characterization was performed by targeted DNA sequencing of 523 cancer-relevant genes. Patients with LDS papilloma (n = 17) and LDS carcinoma (n = 15) were included. There was a male predominance (68%) and a median age at diagnosis of 46.0 years (range 27.5–65.5 years) in patients with papilloma and 63.8 years (range 34.0–87.2 years) in patients with carcinoma. Transcriptional activity of the HPV E6/E7 oncogenes was detected in the whole tumor thickness in 12/15 (80%) papillomas (HPV6, 11, 16) and 10/15 (67%) squamous cell carcinomas (SCC) (HPV11: 3/15 (20%) and HPV16: 7/15 (47%)). Pathogenic variants in PIK3CA, FGFR3, AKT1, and PIK3R1, wildtype TP53, p16 overexpression, and deregulated high-risk E6/E7 transcription characterized the HPV16-positive SCC. The deregulated pattern of HPV E6/E7 expression, correlating with HPV DNA presence and p16 positivity, supports a causal role of HPV in a subset of LDS papillomas and carcinomas. The viral and molecular profile of LDS SCC resembles that of other HPV-driven SCC.
KW - human papillomavirus
KW - lacrimal drainage system
KW - papilloma
KW - squamous cell carcinoma
U2 - 10.3390/cancers14102558
DO - 10.3390/cancers14102558
M3 - Journal article
C2 - 35626161
AN - SCOPUS:85130372227
VL - 14
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 10
M1 - 2558
ER -
ID: 314155885