Discovery of a novel ITPR2::KRAS fusion in large cell neuroendocrine lung cancer: a case report

Background: There are many common gene mutations that occur in lung cancers, including KRAS. KRAS is an oncogene responsible for mediating cell growth through the MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) pathway. ITPR2 is a calcium channel responsible for regulating intracellular calcium levels. This case report highlights the presence and detection of a previously unreported ITPR2::KRAS fusion in a large cell neuroendocrine carcinoma of the lung. Case Description: A 65-year-old patient with a history of smoking developed an aggressive large cell neuroendocrine carcinoma (LCNEC) of the lung. This rare tumor subtype (up to 3% incidence in lung cancer) has a particularly poor prognosis, with a median overall survival of 8–12 months. Additionally, the tumor possessed a previously unreported ITPR2::KRAS fusion, which was a unique event upon examining over 100,000 tumors in public databases. Comorbidities including chronic obstructive pulmonary disease (COPD) and neuropathy presented difficulties in the treatment of this patient due to an inability to undergo surgical resection. The patient was successfully treated with concurrent chemoradiotherapy with carboplatin and etoposide, a first-line chemoradiotherapy. Conclusions: Upon applying relatively unused RNA-fusion tools, this fused ITPR2::KRAS was not projected to yield a functional protein. This supports that post hoc use of bioinformatics tools may support clinical decision making for patients when encountering rare genomic alterations, captured by existing diagnostic tests, that would be perceived as highly oncogenic.