STATISTICAL METHODS FOR THE ANALYSIS OF CANCER GENOME SEQUENCING DATA

The purpose of cancer genome sequencing studies is to determine the nature and types of alterations present in a typical cancer and to discover genes mutated at high frequencies. In this article we discuss statistical methods for the analysis of data generated in these studies. We place special emphasis on a two-stage study design introduced by Sjoblom et al.[1]. In this context, we describe statistical methods for constructing scores that can be used to prioritize candidate genes for further investigation and to assess the statistical signicance of the candidates thus identfied

Serial Analysis of Gene Expression Adapted for Downsized Extracts (SAGE/SADE) Analysis in Reticulocytes

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Somatic mutations of PPP2R1A in ovarian and uterine carcinomas

Exome sequencing of ovarian clear-cell carcinoma has identified somatic mutations in PPP2R1A, a subunit of protein phosphatase 2A. The present study was performed to determine the frequency of PPP2R1A mutations in exon 5, which harbors previously reported mutation hot spots, and adjacent exon 6, in 209 ovarian and 56 uterine tumors of various histologic subtypes. PPP2R1A mutations were demonstrated in 10 of 110 type I ovarian tumors (9.1%) including low-grade serous, low-grade endometrioid, clear-cell, and mucinous carcinomas. In contrast, none of 71 type II ovarian (highgrade serous) carcinomas exhibited PPP2R1A mutations. Moreover, PPP2R1A mutations were observed in 2 of 30 type I uterine (endometrioid) carcinomas (6.7%) and 5 of 26 type II uterine (serous) carcinomas (19.2%). Of the 18 mutations, 13 affected the R182 or 183, and there were 5 novel mutations including 3 involving S256, 1 involving W257, and 1 involving P179. All mutations were located in the \u3b1-helix repeats near the interface between the A subunit and the regulatory B subunit of the enzyme complex. These data provide new evidence that PPP2R1A somatic mutations occur in certain types of uterine and ovarian neoplastic lesions, especially uterine serous carcinomas, and suggest that mutation of PPP2R1A may participate in the pathogenesis of ovarian type I and uterine type II carcinomas

Abundant transcripts of malting barley identified by serial analysis of gene expression (SAGE)

Serial analysis of gene expression (SAGE) was applied to the major cereal crop barley (Hordeum vulgare) to characterize the transcriptional profile of grain during the malting process. Seven SAGE libraries were generated from seed at different time points during malting, in addition to one library from dry mature seed. A total of 155 206 LongSAGE tags, representing 41 909 unique sequences, was generated. This study reports an in-depth analysis of the most abundant transcripts from each of eight specific time points in a malting barley time course. The 100 most abundant tags from each library were analysed to identify the putative functional role of highly abundant transcripts. The largest functional groups included transcripts coding for stress response and cell defence, ribosomal proteins and storage proteins. The most abundant tag represented B22EL8, a barley metallothionein, which showed significant up-regulation across the malting time course. Considerable changes in the abundance profiles of some of the highly abundant tags occurred at 24 h post-steeping, indicating that it may be an important time point for gene expression changes associated with barley seed germination

White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer

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