Copy number gains of FGFR1 and 3q chromosome in squamous cell carcinoma of the lung

Squamous cell carcinoma of the lung (SQCCL) remains a leading cause of cancer-related death. Unlike non-smoker adenocarcinoma of the lung, where highly efficient tyrosine kinase inhibitors are available for treating mutant EGFR or ALK-rearranged, no targetable biomarkers are available for SQCCL. The frequent and focal amplification of FGFR1 has generated great expectations in offering new therapeutical options in case of 16-22% of SQCCL patients.

Broad 3q chromosome amplification is widely recognized as the most common chromosomal aberration found in SQCCL, where PIK3CA, SOX2, ACK1, PRKCI, TP63, PLD1, ECT2, and others genes are located. Although SOX2 has been postulated as a key regulator of basal stem cells transformation and tumor progression, it seems to confer a good prognosis in SQCCL. It is known that each patient might carry a different length of 3q chromosome amplicon. Thus, we suggest that the number and the biological importance of the genes spanned along each patient’s 3q amplicon might help to explain inter-individual outcome variations of the disease and its potential predictive value, especially when relevant oncogenes such as those mentioned above are implicated.

Currently, there is no clinical predictive data available from clinical trials. In this review, we have focused on the potential role of FGFR1 in SQCCL prognosis. Additionally, we have explored recently available public data on the comprehensive genomic characterization of SQCCL, in relation to the protein-coding genes that have a strong gene copy number - mRNA correlation in 3q chromosome, that were previously described as potential driver oncogenes or its modifiers in SQCCL.