57 - Development of a Mate Pair Lineage Assay to Ascertain Relation of Tumors

Abstract

The presence of multiple lesions typically indicates a primary tumor with associated metastases but it is not uncommon for patients to present with multiple synchronous independent primary lesions. Given significant clinical implications, it is important to accurately make this distinction. Recently it was shown that mate pair genomic sequencing can accurately determine relatedness between a patient's multiple synchronous lung carcinomas. Thus, we are designing a clinical mate pair assay to differentiate related from unrelated synchronous tumors, irrespective of type. A variety of tumor types and sets will be collected: 1) multiple separate tissue samples from the same primary tumor; 2) tissue sample from primary tumor and from confirmed metastasis in the same patient; 3) tissue sample from two confirmed independent primary tumors from the same patient. Normal tissue will be sequenced for each patient to exclude germline similarities. Following mate pair sequencing, in-house algorithms will be used for mapping, variant calling, and relatedness. Data analysis will initially follow the method established by Murphy et al. (J Clin Oncol 32:4050–4058) in which a single somatic shared event was diagnostic of lineage. Further discussions of this test will include refinements of the algorithm and false positive rate. The pathologist's assessment of tumor relatedness based on morphology and immunohistochemistry will be the gold standard to determine the accuracy of this assay. The assay will be considered successful if it correctly identifies the lineage of related and unrelated tumors at a high frequency. Additionally, progress to date, challenges, and future steps will be discussed.