TP53 – Oral Cancer News

DNA shed from head and neck tumors detected in blood and saliva

Source: www.medicalexpress.comAuthor: Wang et al., Science Translational Medicine (2015) Schematic showing the shedding of tumor DNA from head and neck cancers into the saliva or plasma. Tumors from various anatomic locations shed DNA fragments containing tumor-specific mutations and human papillomavirus DNA into the saliva or the circulation. The detectability of tumor DNA in the saliva varied with anatomic location of the tumor, with the highest sensitivity for oral cavity cancers. The detectability in plasma varied much less in regard to the tumor’s anatomic location. Credit: Wang et al., Science Translational Medicine (2015) On the hunt for better cancer screening tests, Johns Hopkins scientists led a proof of principle study that successfully identified tumor DNA shed into the blood and saliva of 93 patients with head and neck cancer. A report on the findings is published in the June 24 issue of Science Translational Medicine. "We have shown that tumor DNA in the blood or saliva can successfully be measured for these cancers," says Nishant Agrawal, M.D., associate professor of otolaryngology—head and neck surgery—and of oncology at the Johns Hopkins University School of Medicine. "In our study, testing saliva seemed to be the best way to detect cancers in the oral cavity, and blood tests appeared to find more cancers in the larynx, hypopharynx and oropharynx. However, combining blood and saliva tests may offer the best chance of finding cancer in any of those regions." Agrawal explains that inborn genetic predispositions for most head and neck cancers are rare, but [...]

Oral Cancer Foundation News Team - A2015-06-25T16:43:35-07:00June, 2015|Oral Cancer News|

Certain genetic alterations may explain head and neck cancer survival disparities

Source: www.sciencecodex.com Author: staff Certain genetic alterations to the PAX gene family may be responsible for survival disparities seen between African-American and non-Latino white men with head and neck cancer, according to results presented here at the Sixth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held Dec. 6-9. "During the last 30 years, the overall five-year relative survival rates for head and neck squamous cell carcinoma (HNSCC) have increased, but despite that, the gap in overall survival rates between non-Latino white patients and African-American patients has remained unchanged," said Rafael Guerrero-Preston, Dr.P.H., assistant professor at Johns Hopkins University in Baltimore, Md. "This disparity may be due to differences in genetic and epigenetic alterations among African-American patients." To test this theory, Guerrero-Preston and colleagues performed a two-stage epigenomic study. In the stage-one discovery phase, the researchers used next-generation sequencing and array-based technologies to evaluate 107 HNSCC samples. In the stage-two validation phase, they validated the findings of the discovery phase and evaluated their effect on survival rates in 279 patient samples from The Cancer Genome Atlas project. "Our results highlight the differential genomic and epigenomic alterations in PAX, NOTCH, and TP53 pathways between African-American and non-Latino white HNSCC patients, which underlie the complex biology of morphologically similar tumors and explain HNSCC survival disparities," Guerrero-Preston said. "If further validated in larger cohorts, these discoveries could be used to develop genomic and epigenomic panels that will enable more treatment options, a reduction in treatment [...]

Oral Cancer Foundation News Team - A2013-12-09T14:38:31-07:00December, 2013|Oral Cancer News|

Enhanced radiation sensitivity in HPV-positive head and neck cancer

Source: http://cancerres.aacrjournals.orgAuthors: Randall J. Kimple1,*,Molly A. Smith1,Grace C Blitzer1,Alexandra D Torres1,Joshua A Martin1,Robert Z. Yang1,Chimera R Peet1,Laurel D. Lorenz2,Kwangok P Nickel3,Aloysius J Klingelhutz4,Paul F Lambert5, andPaul M Harari1 Abstract Patients with human papillomavirus associated (HPV+) head and neck cancer (HNC) demonstrate significantly improved survival outcome compared to those with HPV-negative (HPV-) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV- HNC cell lines using in vitro and in vivo techniques. HPV+ HNCs exhibited greater intrinsic radiation sensitivity (average SF2 HPV- 0.59 vs. HPV+ 0.22, p<0.0001), corresponding with a prolonged G2/M cell cycle arrest and increased apoptosis following radiation exposure (percent change 0% vs. 85%, p=0.002). A genome-wide microarray was used to compare gene-expression 24 hours following radiation between HPV+ and HPV- cell lines. Multiple genes in TP53 pathway were upregulated in HPV+ cells (Z score 4.90), including a 4.6 fold increase in TP53 (p<0.0001). Using immortalized human tonsillar epithelial cells, increased radiation sensitivity was seen in cell expressing HPV-16 E6 despite the effect of E6 to degrade p53. This suggested that low levels of normally functioning p53 in HPV+ HNC cells could be activated by radiation, leading to cell death. Consistent with this, more complete knockdown of TP53 by siRNA resulted in radiation resistance. These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV- HNC. This issue is under active investigation in [...]

Charlotte Parker2013-06-10T16:15:32-07:00June, 2013|Oral Cancer News|