Limits...
Genetic Mutation and Exosome Signature of Human Papilloma Virus Associated Oropharyngeal Cancer

View Article: PubMed Central - PubMed

ABSTRACT

Human papilloma virus-16 (HPV-16) associated oropharyngeal cancer (HPVOPC) is increasing alarmingly in the United States. We performed whole genome sequencing of a 44 year old, male HPVOPC subject diagnosed with moderately differentiated tonsillar carcinoma. We identified new somatic mutation in MUC16 (A.k.a. CA-125), MUC12, MUC4, MUC6, MUC2, SIRPA, HLA-DRB1, HLA-A and HLA-B molecules. Increased protein expression of MUC16, SIRPA and decreased expression of HLA-DRB1 was further demonstrated in this HPVOPC subject and an additional set of 15 HPVOPC cases. Copy number gain (3 copies) was also observed for MUC2, MUC4, MUC6 and SIRPA. Enhanced expression of MUC16, SIRPA and HPV-16-E7 protein was detectable in the circulating exosomes of numerous HPVOPC subjects. Treatment of non-tumorigenic mammary epithelial cells with exosomes derived from aggressive HPVOPC cells harboring MUC16, SIRPA and HPV-16-E7 proteins augmented invasion and induced epithelial to mesenchymal transition (EMT) accompanied by an increased expression ratio of the EMT markers Vimentin/E-cadherin. Exosome based screening of key HPVOPC associated molecules could be beneficial for early cancer diagnosis, monitoring and surveillance.

No MeSH data available.


Related in: MedlinePlus

Expression pattern of MUC16, SIRPA and HLA-DRB1 in the primary HPVOPC tissues.Compared to the matched normal counterparts, high expression of MUC16 (a) and SIRPA (b) in both the dysplasia and cancer tissues (arrowheads). The expression of MUC16 in the cancer tissues was both membrane bound (black arrowhead) and secretory (red arrowhead). The expression of HLA-DRB1 was barely detectable (p = 0.0002) in the cancerous tissues (encircled) compared to the matched normal tonsillar tissues (c). Image magnification X 200.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5382706&req=5

f3: Expression pattern of MUC16, SIRPA and HLA-DRB1 in the primary HPVOPC tissues.Compared to the matched normal counterparts, high expression of MUC16 (a) and SIRPA (b) in both the dysplasia and cancer tissues (arrowheads). The expression of MUC16 in the cancer tissues was both membrane bound (black arrowhead) and secretory (red arrowhead). The expression of HLA-DRB1 was barely detectable (p = 0.0002) in the cancerous tissues (encircled) compared to the matched normal tonsillar tissues (c). Image magnification X 200.

Mentions: To examine the corresponding protein expression pattern of some of the genes exhibiting somatic mutations, we performed immunohistochemistry (IHC) using antibodies specific for MUC16, SIRPA and HLA-DRB1 on paired normal and malignant FFPE tissue samples obtained from this HPVOPC subject. We observed an exclusively abundant expression of MUC16 and SIRPA in the dysplastic lesions and the corresponding carcinoma tissues of this patient (Fig. 3a,b). The expression of MUC16 and SIRPA was barely detectable in the cancer adjacent normal tissues (Fig. 3a,b). The expression pattern of MUC16 and SIRPA appears to be both membrane bound (black arrowheads) and secretory (red arrowheads) (Fig. 3a,b). On the other hand, marked loss (p = 0.0002) of HLA-DRB1 expression was evident in the tumor tissues compared to the normal tonsillar tissues (Fig. 3c). Appreciable expression of HLA-DRB1 was evident in tumor adjacent normal appearing tonsillar tissues (Fig. 3c, black arrowheads).


Genetic Mutation and Exosome Signature of Human Papilloma Virus Associated Oropharyngeal Cancer
Expression pattern of MUC16, SIRPA and HLA-DRB1 in the primary HPVOPC tissues.Compared to the matched normal counterparts, high expression of MUC16 (a) and SIRPA (b) in both the dysplasia and cancer tissues (arrowheads). The expression of MUC16 in the cancer tissues was both membrane bound (black arrowhead) and secretory (red arrowhead). The expression of HLA-DRB1 was barely detectable (p = 0.0002) in the cancerous tissues (encircled) compared to the matched normal tonsillar tissues (c). Image magnification X 200.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382706&req=5

f3: Expression pattern of MUC16, SIRPA and HLA-DRB1 in the primary HPVOPC tissues.Compared to the matched normal counterparts, high expression of MUC16 (a) and SIRPA (b) in both the dysplasia and cancer tissues (arrowheads). The expression of MUC16 in the cancer tissues was both membrane bound (black arrowhead) and secretory (red arrowhead). The expression of HLA-DRB1 was barely detectable (p = 0.0002) in the cancerous tissues (encircled) compared to the matched normal tonsillar tissues (c). Image magnification X 200.
Mentions: To examine the corresponding protein expression pattern of some of the genes exhibiting somatic mutations, we performed immunohistochemistry (IHC) using antibodies specific for MUC16, SIRPA and HLA-DRB1 on paired normal and malignant FFPE tissue samples obtained from this HPVOPC subject. We observed an exclusively abundant expression of MUC16 and SIRPA in the dysplastic lesions and the corresponding carcinoma tissues of this patient (Fig. 3a,b). The expression of MUC16 and SIRPA was barely detectable in the cancer adjacent normal tissues (Fig. 3a,b). The expression pattern of MUC16 and SIRPA appears to be both membrane bound (black arrowheads) and secretory (red arrowheads) (Fig. 3a,b). On the other hand, marked loss (p = 0.0002) of HLA-DRB1 expression was evident in the tumor tissues compared to the normal tonsillar tissues (Fig. 3c). Appreciable expression of HLA-DRB1 was evident in tumor adjacent normal appearing tonsillar tissues (Fig. 3c, black arrowheads).

View Article: PubMed Central - PubMed

ABSTRACT

Human papilloma virus-16 (HPV-16) associated oropharyngeal cancer (HPVOPC) is increasing alarmingly in the United States. We performed whole genome sequencing of a 44 year old, male HPVOPC subject diagnosed with moderately differentiated tonsillar carcinoma. We identified new somatic mutation in MUC16 (A.k.a. CA-125), MUC12, MUC4, MUC6, MUC2, SIRPA, HLA-DRB1, HLA-A and HLA-B molecules. Increased protein expression of MUC16, SIRPA and decreased expression of HLA-DRB1 was further demonstrated in this HPVOPC subject and an additional set of 15 HPVOPC cases. Copy number gain (3 copies) was also observed for MUC2, MUC4, MUC6 and SIRPA. Enhanced expression of MUC16, SIRPA and HPV-16-E7 protein was detectable in the circulating exosomes of numerous HPVOPC subjects. Treatment of non-tumorigenic mammary epithelial cells with exosomes derived from aggressive HPVOPC cells harboring MUC16, SIRPA and HPV-16-E7 proteins augmented invasion and induced epithelial to mesenchymal transition (EMT) accompanied by an increased expression ratio of the EMT markers Vimentin/E-cadherin. Exosome based screening of key HPVOPC associated molecules could be beneficial for early cancer diagnosis, monitoring and surveillance.

No MeSH data available.


Related in: MedlinePlus