Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer

Abstract

Genetic events specific to the pathogenesis of malignancy can offer clues to the tumorigenesis process. The objective of this study was to identify gene alterations that differentiate tumor and nontumor lesions in squamous head and neck cancer (HNSCC). DNA from 220 primary HNSCC with concurrently present tumor and nontumor lesions from the same patient was interrogated for genomic alterations of loss or gain of copy. Conditional logistic regression dealt with tumor and non-tumor records within a patient. Of 113 genes, 53 had univariate effects (P < 0.01), of which 16 genes remained in the multivariable model with P < 0.01. The model had a C-index (ROC) of 0.93. Loss of CDKN2B and gain of BCL6, FGF3, and PTP4A3 predicted tumor. Loss of BAK1 and CCND1 and gain of STCH predicted nontumor. This highly powered model assigned alterations in 16 genes specific for malignant versus nonmalignant lesions, supporting their contribution to the pathogenesis of HNSCC as well as their potential utility as relevant targets for further evaluation as markers of early detection and progression.

Hypomethylated Fgf3 is a potential biomarker for early detection of oral cancer in mice treated with the tobacco carcinogen dibenzo[def,p]chrysene

“…Fgf3 has the most prominent gene expression changes among all the genes examined by RT-PCR and has been reported to be amplified in head and neck cancers [ 36 – 38 ]. To examine if hypomethylation and gene amplification of Fgf3 will also result in changes in protein expression, FGF3 expression was examined by immunohistochemistry.…”

High expressions of BCL6 and Lewis y antigen are correlated with high tumor burden and poor prognosis in epithelial ovarian cancer

“…27 Based on these findings, BCL6 inhibitors (compound 79-6 28 or retroinverso BCL6 peptide inhibitor (RI-BPI) 29 ) have been developed and showed delightful potential application prospect as a therapeutic strategy for patients with hematological malignancies. 28,29 In recent years, overexpression of BCL6 was reported to be relevant to somatic malignant tumors, such as gastric cancer, 6 gallbladder cancer, 7 breast cancer, 8 colorectal cancer, 9 and head and neck cancer, 10 suggesting that the tumorigenicity of BCL6 is not only limited to lymphomas. BCL6 protein was highly expressed both in cell lines and tissue specimens of breast cancer 8 and it enhanced the proliferation, growth, migration and survival of breast cancer cells through the regulation of epithelial-mesenchymal transition (EMT) by enhancing the expression of ZEB1 which bound to the E-cadherin promoter and repressing the E-cadherin transcription.…”

“…B-cell CLL/lymphoma 6 (BCL6), a highly conserved zinc finger (ZF) transcriptional factor, was first identified as an oncogene by gene expression profile in non-Hodgkin's lymphoma in 2000; 3 it exhibits pivotal roles in germinal center formation and regulation of lymphocyte function, differentiation, and survival. 4 In recent years, more and more studies identified that BCL6 was overexpressed not only in B-cell lymphoma 5 but also in gastric cancer, 6 gallbladder cancer, 7 breast cancer, 8 colorectal cancer, 9 head and neck cancer, 10 and so on. However, there are quite a few studies on the function of BCL6 in ovarian cancer, and it remains unclear whether BCL6 may aberrantly express or be a potential prognosis marker in ovarian cancer.…”

Chaperone Stress 70 Protein (STCH) Binds and Regulates Two Acid/Base Transporters NBCe1-B and NHE1 *

“…STCH-related Pathologies-Recent studies have reported that STCH is a candidate gene involved in certain cancers (20,33,34) as well as several central nervous system pathologies (16 -18). Our new description of the STCH chaperone as a pH i regulator points to several potential consequences of its malfunction that may shed light on these reports.…”