Dataset Information

Codon-level co-occurrences of germline variants and somatic mutations in cancer are rare but often lead to incorrect variant annotation and underestimated impact prediction.

ABSTRACT: Cancer cells explore a broad mutational landscape, bringing the possibility that tumor-specific somatic mutations could fall in the same codons as germline SNVs and leverage their presence to produce substitutions with a larger impact on protein function. While multiple, temporally consecutive mutations to the same codon have in the past been detected in the germline, this phenomenon has not yet been explored in the context of germline-somatic variant co-occurrences during cancer development. We examined germline context at somatic mutation sites for 1395 patients across four cancer cohorts (breast, skin, colon, and head and neck) and found 392 codon-level co-occurrences between germline and somatic variants, including over a dozen in well-known cancer genes. We found that for the majority of these co-occurrence events, traditional somatic calling led to an inaccurate representation of the protein site and a significantly lower predicted impact on protein fitness. We conclude that these events often lead to imprecise annotation of somatic variants but do not appear to be a frequent source of driver events during cancer development.

SUBMITTER: Koire A

PROVIDER: S-EPMC5370158 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Codon-level co-occurrences of germline variants and somatic mutations in cancer are rare but often lead to incorrect variant annotation and underestimated impact prediction.

Koire Amanda A Kim Young Won YW Wang Jarey J Katsonis Panagiotis P Jin Haijing H Lichtarge Olivier O

PloS one 20170328 3

Cancer cells explore a broad mutational landscape, bringing the possibility that tumor-specific somatic mutations could fall in the same codons as germline SNVs and leverage their presence to produce substitutions with a larger impact on protein function. While multiple, temporally consecutive mutations to the same codon have in the past been detected in the germline, this phenomenon has not yet been explored in the context of germline-somatic variant co-occurrences during cancer development. We ...[more]

PMID: 28350864

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Project description:BACKGROUND:Left ventricular mass normalization for body size is recommended, but a question remains: what is the best body size variable for this normalization-body surface area, height or lean body mass computed based on a predictive equation? Since body surface area and computed lean body mass are derivatives of body mass, normalizing for them may result in underestimation of left ventricular mass in overweight children. The aim of this study is to indicate which of the body size variables normalize left ventricular mass without underestimating it in overweight children. METHODS:Left ventricular mass assessed by echocardiography, height and body mass were collected for 464 healthy boys, 5-18 years old. Lean body mass and body surface area were calculated. Left ventricular mass z-scores computed based on reference data, developed for height, body surface area and lean body mass, were compared between overweight and non-overweight children. The next step was a comparison of paired samples of expected left ventricular mass, estimated for each normalizing variable based on two allometric equations-the first developed for overweight children, the second for children of normal body mass. RESULTS:The mean of left ventricular mass z-scores is higher in overweight children compared to non-overweight children for normative data based on height (0.36 vs. 0.00) and lower for normative data based on body surface area (-0.64 vs. 0.00). Left ventricular mass estimated normalizing for height, based on the equation for overweight children, is higher in overweight children (128.12 vs. 118.40); however, masses estimated normalizing for body surface area and lean body mass, based on equations for overweight children, are lower in overweight children (109.71 vs. 122.08 and 118.46 vs. 120.56, respectively). CONCLUSION:Normalization for body surface area and for computed lean body mass, but not for height, underestimates left ventricular mass in overweight children.

Dataset Information

Codon-level co-occurrences of germline variants and somatic mutations in cancer are rare but often lead to incorrect variant annotation and underestimated impact prediction.

Publications

Codon-level co-occurrences of germline variants and somatic mutations in cancer are rare but often lead to incorrect variant annotation and underestimated impact prediction.

Similar Datasets

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