De novo methylation of tumor suppressor gene p16/INK4a is a frequent finding in multiple myeloma patients at diagnosis.

The p16 gene competes with cyclin D for binding to CDK4/CDK6 and therefore inhibits CDK4/6 complex kinase activity, resulting in dephosphorylation of pRb and related G1 growth arrest. Inactivation of this gene has been involved in a variety of tumors by different mechanisms: homozygous/hemyzygous deletions, point mutations and methylation of a 5' CpG island into exon E1alpha of the p16 gene. Homozygous deletions have been rarely found in multiple myeloma (MM) and no point mutations have been reported. Two recent studies have reported a high prevalence of methylation in the exon E1alpha of the p16 gene, but included only a small number of cases. We have analyzed the methylation pattern of exon E1alpha of the p16 gene in 101 untreated MM and five primary plasma cell leukemias (PCL). A PCR assay, relying on the inability of some restriction enzymes to digest methylated sequences, was used to analyze the methylation status. Southern blot analysis was used to confirm these results. Forty-one of 101 MM patients (40.5%) as well as four of the five (80%) primary PCL patients had shown methylation of the exon E1alpha. Our study confirms that hypermethylation of the p16 gene is a frequent event in MM. Leukemia (2000) 14, 183-187.

Finding a Scientific Voice: Performing Science, Space and Speech in the Nineteenth Century

Taking as a point of departure recent scholarly interest in the geographies of spoken communication, this paper situates the cultivation of a scientific voice in a range of nineteenth-century contexts and locations. An examination of two of the century’s most celebrated science lecturers, Michael Faraday and Thomas Henry Huxley, offers a basis for more general claims about historical relations between science, speech and space. The paper begins with a survey of the ‘ecologies’ of public speaking in which advocates of science sought to carve out an effective niche. It then turns to a reconstruction of the varying and variously interpreted assumptions about authoritative and authentic speech that shaped how the platform performances of Faraday and Huxley were constructed, contested and remediated in print. Particular attention is paid to sometimes clashing ideals of vocal performance and paralinguistic communication. This signals an interest in the performative 2 dimensions of science lectures rather more than their specific cognitive content. In exploring these concerns, the paper argues that ‘finding a scientific voice’ was a fundamentally geographical enterprise driven by attempts to make science resonate with a wider oratorical culture without losing distinctive appeal and special authority