Anti-MIB2 monoclonal antibody, clone 2C6

A family with an aggregation of rare early onset multiple primary tumors has been managed in our oncogenetics department: the proband developed four early onset carcinomas between ages 31 and 33 years, including acral melanoma, bilateral clear cell renal carcinoma (RC), and follicular variant of papillary thyroid carcinoma. The proband's parent developed orbital lymphoma and small intestine mucosa-associated lymphoid tissue (MALT) lymphoma between 40 and 50 years old. Whole-exome-sequencing (WES) of the nuclear family (proband, parents, and sibling) identified in the proband a de novo deleterious heterozygous mutation c.1003C > T (p.Arg335*) in the phosphatase and tensin homolog (PTEN) gene. Furthermore, WES allowed analysis of the nuclear family's genetic background, and identified deleterious variants in two candidate modifier genes: CEACAM1 and MIB2. CEACAM1, a tumor suppressor gene, presents loss of expression in clear cell RC and is involved in proliferation of B cells. It could explain in part the phenotype of proband's parent and the occurrence of clear cell RC in the proband. Deleterious mutations in the MIB2 gene are associated with melanoma invasion, and could explain the occurrence of melanoma in the proband. Cowden syndrome is a hereditary autosomal dominant disorder associated with increased risk of mucocutaneous features, hamartomatous tumors, and cancer. This atypical presentation, including absence of muco-cutaneous lesions, four primary early onset tumors and bilateral clear cell RC, has not been described before. This encourages including the PTEN gene in panel testing in the context of early onset RC, whatever the histological subtype. Further studies are required to determine the implication of CEACAM1 and MIB2 in the severity of Cowden syndrome in our proband and occurrence of early onset MALT lymphoma in a parent.

Algorithms for real-time performance management and adaptive fault/anomaly detection in Internet protocol (IP) networks and services have been developed, and a corresponding real-time distributed software platform has been implemented. These algorithms automatically and adaptively detect "soft" faults or anomalies (performance degradations) in IP networks and services, enabling timely correction of network exceptions before failures occur and services are compromised and thereby achieving proactive network and service management. Further these algorithms are implemented as a reliable, fully distributed real-time software platform-the network/service anomaly detector (NSAD)-with the following features. First, it provides a flexible platform on which preconstructed monitoring and detection components can be mixed, matched, and distributed to form a wide range of application-specific NSADs and performance monitors. Second, NSAD and its components can auto-recover in real time, making it a reliable system for persistent monitoring of networks and their services. Third, anomaly detection is performed on raw network observables-for example, performance data such as management information base-2 (MIB2) and remote monitor-1/2 (RMON1/2) variables-and algebraic functions of these observables (objective functions), thereby enabling objective-driven anomaly detection of wide range and high sensitivity. Fourth, controlled testing (with anomalies injected a priori into a test network) demonstrates that NSAD can detect anomalies reliably in IP networks. Thus, NSAD provides a powerful framework/platform for automatic, proactive fault/anomaly defection and performance management in IP networks and services.