NEW YORK (GenomeWeb) – Researchers from Bosnia and Herzegovina, the US, and Qatar tracked down potential protein markers for treatment response or resistance in olfactory neuroblastoma during a multi-omics analysis of the rare nasal cancer.
"We identified multiple protein biomarkers of response or resistance to classic chemotherapy and targeted therapy that could be useful in optimizing the cytotoxic chemotherapy and further improving personalized treatment of [olfactory neuroblastoma]," senior author Semir Vranic, a researcher affiliated with the University of Sarajevo and Qatar University, and his colleagues wrote in PLOS One yesterday.
The team, which included investigators from Caris Life Sciences, used a combination of targeted sequencing, gene fusion analyses, array-based expression profiling, copy number assays, and/or immunohistochemistry to assess tumor samples from 23 individuals with advanced or metastatic forms of olfactory neuroblastoma. Along with recurrently mutated genes — which turned up in more than 60 percent of the tumors tested — they identified a few dozen genes that tended to be dialed up or down in the olfactory neuroblastomas.
The researchers also uncovered lower- or higher-than-usual levels of proteins previously implicated in response or resistance to several chemotherapeutic drugs. Moreover, the molecular profiles made it possible to pick up alterations that might be amenable to targeted treatment, including Wnt signaling pathway changes.
"Considering the lack of standardized treatment guidelines, the potential advantages of targeted therapy approaches, and the paucity of data exploring the molecular pathogenesis of [olfactory neuroblastoma], we explored potentially targetable biomarkers/pathways in a cohort of recurrent or metastatic [olfactory neuroblastomas], using [a] multi-platform molecular profiling approach," the authors noted.
To that end, collaborators at a Caris Life Sciences CLIA-certified lab retrospectively analyzed 23 formalin-fixed paraffin-embedded samples collected between 2012 and 2017 from 10 male and 13 female olfactory neuroblastoma patients between the ages of 29 and 84 with recurrent or metastatic forms of the disease.
For 10 of the olfactory neuroblastoma tumors, they did Sanger or Illumina MiSeq sequencing on a panel of 46 genes previously implicated in cancer. Five more tumors were assessed using a broader 592-gene sequencing panel.
The team also used the MiSeq instrument, in combination with an Archer FusionPlex solid tumor kit, to profile gene fusions in half a dozen olfactory neuroblastomas, while genome-wide expression patterns were assessed with Illumina arrays in four tumors. For a subset of tumors, the group used fluorescence in situ hybridization or chromogenic in situ hybridization to interrogate copy number patterns for genes such as EGFR, HER2, and cMET.
The researchers detected suspicious mutations in cancer-related genes such as TP53, EGFR, or CTNNB1 in 63 percent of the olfactory neuroblastoma tumors tested. In the tumors assessed with genome-wide expression arrays, meanwhile, they described 21 over-expression genes and 19 genes with muted expression in the olfactory neuroblastomas.
When the authors turned to immunohistochemistry to assess levels of 25 previously reported protein markers in the olfactory neuroblastoma tumors, it saw cases with marked changes in protein biomarkers linked to cisplatin, irinotecan, or vincristine response. On the other hand, they detected little to no expression of immune checkpoint proteins such as PD-1 or PD-L1, prompting them to suggest that the "therapeutic benefits of immune checkpoint inhibitors are less likely."