Genomic alterations on 8p21-p23 are the most frequent genetic events in stage I squamous cell carcinoma of the lung

Abstract

Genetic alterations in the early stages of cancer have a close correlation with tumor initiation and potentially activate downstream pathways implicated in tumor progression; however, the method of initiation in sporadic neoplasias is largely unknown. In this study, whole-genome microarray-comparative genomic hybridization was performed to identify the early genetic alterations that define the prognosis of patients with stage I squamous cell carcinoma (SCC) of the lung. The most striking finding was the high frequency of copy number losses and hemizygous deletions on chromosome 8p, which occurred in 94.7% (18/19) and 63.2% (12/19) of the cases, respectively, with a delineated minimal common region of 8p21.1-p23.3. More specifically, three loci of homozygous deletions at 8p23.1 were noted in 21.1% (4/19) of the cases. This region contains the following possible target genes, which have previously not been implicated to play a pathogenic role in stage I SCCs: MSRA, MFHAS1, CLDN23, DEFB106A, DEFB105A, LOC441316, FAM90A7P and LOC441318. These findings indicate that genetic alterations on chromosome 8p may be the first step in the initiation of genomic instability in early SCCs, and the newly identified genes in the 8p23.1 chromosomal region might be of interest for the study of the pathophysiology of stage I SCC, as potential targets for therapeutic measures.

Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients

“…Higher frequency of 8p23.1 loss was found to be significant in the CHOICE study. Genes in this region, such as MSRA , MFHAS1 , DEFB106A , and DEFB105A , play an important role in the initiation and progression of lung SQCC 22 . Focal alteration at 14q11.2 containing olfactory receptor family genes was specifically identified in lung ADC.…”

Genomewide profiling of copy‐number alteration in monoclonal gammopathy of undetermined significance

“…Loss at 1p, mainly deletion of FAM46C and CDKN2C, has been shown to be associated with adverse prognosis in MM (26)(27)(28) and also with progression of SMM to MM (29). It has been shown that 8p loss plays an important role in the pathogenesis of various tumor disorders (30)(31)(32). However, impact on survival of MM patients was not found in a previous study (33).…”

Association of expression quantitative trait loci for long noncoding RNAs with lung cancer risk in Asians

“…Rs1600249, located at chromosome region 8p23.1, is 394KB away from AF131215.2 . Genetic alterations in the distal part of 8p21.1‐p23.3 frequently occur in the early stage of lung cancer . Meanwhile, the size of these alterations, as well as their frequency, tends to increase during lung cancer progression .…”

“…Genetic alterations in the distal part of 8p21.1-p23.3 frequently occur in the early stage of lung cancer. 59 Meanwhile, the size of these alterations, as well as their frequency, tends to increase during lung cancer progression. 60,61 Coexpressed genes with AF131215.2 were mainly enriched in the thyroid hormone signaling pathway.…”