RUNX1T1 Amplification Induces "Small Cell" Cancer
Abstract
Small cell lung cancer (SCLC) is one of the deadliest cancers encountered by oncologists, with 5-year survival rates of less than 2% for patients with metastatic disease. Current thinking is that small cell lung cancer (SCLC) arises from a small population of specific neuroendocrine-like cells in the lung and is driven principally by concurrent mutation of two genes, TP53 and RB1. While this maybe true for the majority of 'every-day SCLC patients, there are two other clinically-important subgroups of cancer patients with small cell disease; so-called combined small cell lung cancer and extra-pulmonary small cell cancer. In combined SCLC the tumors consist of both a SCLC component and a second subtype of lung cancer, such as adenocarcinoma, and it is believed that the second, more differentiated component has transformed into a small cell cancer. Similarly, extra-pulmonary small cell tumors have primary tumors that arise outside the lung, such as in the prostate or GI tract, and transform into a small cell cancer. So in reality the term small cell simply describes a microscopic appearance, or phenotype. Clinically, however, this small cell phenotype is of great importance because it is treated the same, regardless of whether it is pulmonary, combined or extra-pulmonary and predicts the same aggressive disease course with high mortality. Here we seek to validate one potential pathway leading to the formation of a small cell phenotype: through amplification of a gene called RUNX1T1, which we observed only in the small cell component of two combined SCLC tumors. We will do this by investigating more combined SCLC tumors for RUNX1T1 amplification, as well as by over-expressing RUNX1T1 in various cancer cell lines to see if it transforms them into a small cell phenotype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2018
- Accession Number
- AD1094953
Entities
People
- Afshin Dowlati
Organizations
- Case Western Reserve University