Clonal hematopoiesis of indeterminate potential (CHIP) mutations in solid tumor malignancies.

person Madison Conces Cleveland Clinic, Cleveland, OH info_outline Madison Conces, Ying Ni, Peter Bazeley, Bhumika Patel, Pauline Funchain, Hetty E Carraway

Authors person Madison Conces Cleveland Clinic, Cleveland, OH info_outline Madison Conces, Ying Ni, Peter Bazeley, Bhumika Patel, Pauline Funchain, Hetty E Carraway Organizations Cleveland Clinic, Cleveland, OH, Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Cleveland, OH, Leukemia Program, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH Abstract Disclosures Research Funding Other Background: CHIP predisposes to a higher risk of developing hematological malignancies and cardiac events. Multiple germline mutations have been recognized as contributing to CHIP, most notably ASXL1 , DNMT3A , and TET2 . The frequency of CHIP mutations in solid tumor malignancies (STM) is unknown. We report the frequency and incidence of CHIP mutations in adult patients (pts) with STM. Methods: Data from 880 pts with STM who underwent next generation sequencing (NGS) at Foundation One from 2013-2017 was collected. This excluded two pts with known primary hematological malignancies who were removed. A list of CHIP mutations using NCCN guidelines as well as numerous original research articles was created, and tabulation of pathogenic or likely pathogenic mutations ( ASXL1, DNMT3A, TET2, JAK2, SF3B1, TP53, GNAS, N/KRAS ) was performed. To date, only the lung, breast, and colorectal cancer pts have been annotated (N = 372) since these cancers have an overall higher incidence and prevalence in society. Results: Annotation of lung cancer pts (155/880), breast (118/880), and colorectal cancer pts (99/880) is collected and represents about 40% of all pts. At least one CHIP mutation was present in 44.5% (69/155) lung cancer pts, 32.2% (38/118) in breast cancer pts, and 7.1% (7/99) in colorectal cancer pts. Most common mutations found were TP53 and KRAS at 29.6% (110/372) and 28.0% (104/372), respectively. Mutations in genes not known to be somatic drivers for solid tumor malignancies, particularly SF3B1, DNMT3A , and JAK2 , were found at very low frequencies 0.8% (3/372), 0.5% (2/372), and 0.3% (1/372), respectively. Notably, ASXL1 and TET2 mutations were not encountered in any pts. Conclusions: In tumor NGS testing, multiple CHIP mutations were noted to be present within the cohort of lung, breast, and colorectal cancers. There is a need to further understand clinical consequences of CHIP mutations incidentally found in pts with STM given known clinical implications of CHIP. We will report on clinical data (comorbidities), response/non-response to therapy, and identify specific molecular patterns of mutations to further understand the role of CHIP in pts with STM.