How to Assess the Clinical Relevance of Novel RET Missense Variants in the Absence of Functional Studies?

Introduction And Background: Familial medullary thyroid cancer (FMTC) is caused by gain of function mutations in the proto-oncogene RET (rearranged during transfection). Missense mutations within exon 14 including p.Val804Met are known to cause FMTC and multiple endocrine neoplasia type 2a/b.

LIS1-associated classic lissencephaly: A retrospective, multicenter survey of the epileptogenic phenotype and response to antiepileptic drugs.

Background: Patients with LIS1-associated classic lissencephaly typically present with severe psychomotor retardation and drug-resistant epilepsy within the first year.

Aim: To analyze the epileptogenic phenotype and response to antiepileptic therapy in LIS1-associated classic lissencephaly.

Method: Retrospective evaluation of 22 patients (8 months-24 years) with genetically and radiologically confirmed LIS1-associated classic lissencephaly in 16 study centers.

Understanding tumor heterogeneity as functional compartments--superorganisms revisited.

Compelling evidence broadens our understanding of tumors as highly heterogeneous populations derived from one common progenitor. In this review we portray various stages of tumorigenesis, tumor progression, self-seeding and metastasis in analogy to the superorganisms of insect societies to exemplify the highly complex architecture of a neoplasm as a system of functional "castes."Accordingly, we propose a model in which clonal expansion and cumulative acquisition of genetic alterations produce tumor compartments each equipped with distinct traits and thus distinct functions that cooperate to establish clinically apparent tumors.