Germline SDHB Mutations are Common in Patients With Apparently Sporadic Sympathetic Paragangliomas
Bibliographic record
Abstract
Germline mutations in the genes encoding the B (SDHB) and D (SDHD) subunits of the heterotetrameric protein succinate dehydrogenase (mitochondrial complex II) are important causes of inherited and apparently sporadic paragangliomas. In an effort to further investigate the role of these genes in malignant sympathetic paragangliomas and adrenal pheochromocytomas, we screened a series of tumors for mutations in SDHB and SDHD. Mutation testing was performed on DNA extracted from formalin-fixed, paraffin-embedded tumors and associated normal tissues by polymerase chain reaction amplification and direct sequencing of the coding regions and intron-exon junctions of the SDHB and SDHD genes. Among 16 malignant paragangliomas with proven metastases, 6 (38%) had mutations in SDHB (2 nonsense, 1 splice site, 1 insertion causing a frameshift, and 2 presumably deleterious missense mutations). Probable deleterious SDHB variants were also detected in 5 (45%) of 11 paragangliomas without known metastatic disease (1 splice site, 1 deletion causing a frameshift, and 3 missense changes). In 12 malignant pheochromocytomas, 1 SDHD and no SDHB mutations were identified. The identical SDHB mutation was detected in DNA extracted from accompanying normal tissue for each of the 10 cases on which this analysis was performed. An excess of SDHB mutations in paragangliomas versus pheochromocytomas was found, with no difference in the frequency of mutations in malignant versus benign paragangliomas. The disparate mutational spectra in malignant paragangliomas and pheochromocytomas may reflect differences in underlying tumor biology.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".