Northeastern University


Data Science & Biochemistry, '24

Evaluating the Oncogene-specific Dependency of TIMM17A and MTCH2 in MYC-amplified Cancers

Mentor: William Hahn, M.D.

Institution: Dana Farber Cancer Institute

Amplification of the MYC oncogene is found in nearly 30% of all cancers – regardless of lineage.  Unfortunately, to date, MYC is considered an undruggable oncogene. One method to target the MYC oncogene is to determine the downstream genetic dependencies, or genes that are MYC depends on to facilitate tumorigenesis. Through genome wide screening conducted in MYC-amplified mammary epithelial cells, two target genes, TIMM17A and MTCH2, which encode mitochondrial membrane transport proteins, were identified as MYC-specific genetic dependencies. Furthermore, using MYC amplified human mammary epithelial cells (HMECs), an increase in N-acetylaspartate (NAA) was found to correlate withTIMM17A and MTCH2 expression. This correlation leads us to believe that MYC is dependent on TIMM17A and MTCH2 to drive a metabolic shift, resulting in downstream NAA production.We will analyze the MYC-specific dependency of these two genes, and subsequent downstream production of NAA, in established cell-line models of triple-negative breast cancer and lung cancers. This research will lead to alternative pharmacological approaches to treat cancers with MYC amplification.