Wenbin Mei

Suppl. Figure 6 showing AMIGO2 promotes HIF1a nuclear retention via specific HIF1a residues

Suppl. Figure 3 showing NPTX1 is over-expressed in human primary and metastatic PDAC tumors

Suppl. Figure 1 showing NPTX1 is highly expressed in both human and murine highly metastatic PDAC models.

Suppl. Figure 5 showing AMIGO2 as a cell surface receptor for NPTX1 and a driver of PDAC metastasis

Key resource table with cat numbers

Suppl. Figure 2 showing NPTX1 drives liver metastasis of PDAC

Suppl. Figure 4 showing NPTX1 promotes cell growth under hypoxic conditions

Suppl. figure 7 showing therapeutic targeting of NPTX1 with monoclonal NPTX1 antibody

Cancer frequently clusters in families due to shared environment and genetics. However, many familial cancer cases lack a clinically recognized pathogenic germline variant (PGV). We analyzed germline genomes and family history from 2,726 individuals without a PGV in the All of Us Research Program, including 1,496 cases across 18 cancer types with extensive family history and 1,230 family history-negative, cancer-free controls. We identified allelic series of rare structural variants inactivating MSH2 in individuals with phenotypes consistent with Lynch syndrome and BRCA1 in breast cancer. Cancer polygenic risk scores were enriched in cases and correlated with patterns of cancer diagnoses within families. Exome-wide rare variant analyses nominated six candidate predisposition genes, including TSTD2 and BRAT1 in thyroid and breast cancer, respectively. Overall, polygenic risk and rare variants impacting known genes explained a median of 5% of unexplained familial cancers, increasing to 11% when including newly nominated risk factors.