CoChat
Sign Up
Cited by 215Adrenal and Paraganglionic TumorsMetabolism and Genetic DisordersGastrointestinal Tumor Research and Treatment

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

Succinate dehydrogenase (SDH) and mitochondrial driven neoplasia

Gill, Anthony J.·2012·Pathology
DOI 10.1097/pat.0b013e3283539932
Open this paper in CoChat — free account

Abstract

The genes for the succinate dehydrogenase (SDH) subunits SDHA, SDHB, SDHC and SDHD are encoded in the autosome. The proteins are assembled in the mitochondria to form the mitochondrial complex 2, a key respiratory enzyme which links the Krebs cycle and the electron transport chain. Thirty percent of phaeochromocytoma and paraganglioma (PHEO/PGL) are hereditary and perhaps as many as half of these familial cases are caused by germline mutations of the SDH subunits. Negative immunohistochemical staining for the SDHB subunit identifies PHEO/PGL associated with germline mutation of any of the mitochondrial complex 2 components and can be used to triage formal genetic testing of all PHEO/PGL for SDH mutations. PHEO/PGL associated with SDHA mutation also show negative staining for SDHA as well as SDHB.A unique subgroup of gastrointestinal stromal tumours (GISTs) are driven by mitochondrial complex 2 dysfunction. These SDH deficient GISTs can also be definitively identified by negative staining for SDHB and show distinct clinical and morphological features including frequent onset in childhood and young adulthood, gastric location, a tendency to multifocality, absence of KIT and PDGFRA mutations, a prognosis not predicted by size and mitotic rate and a tendency to indolent behaviour of metastases. Some of these SDH deficient GISTs are driven by classical SDH mutations, but the precise mechanisms of tumourigenesis in many (including those associated with the Carney triad) remain unknown. Germline SDHB mutation is associated with a newly recognised type of renal carcinoma which commonly but not always demonstrates distinctive morphology and can also be recognised by negative staining for SDHB.Immunohistochemistry for SDHB therefore has emerged as a useful tool to recognise these distinct neoplasias driven by mitochondrial complex 2 dysfunction and to triage formal genetic testing for the associated syndromes.

Overview

Integrity signals

Registry

Crossref · 10.1097/pat.0b013e3283539932

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 46 references

Research works printed but not linked: 2

  1. Burnichon, 2010, SDHA is a tumor suppressor gene causing paraganglioma, Hum Mol Genet, 19, 3011, 10.1093/hmg/ddq206 · DOI
  2. Walter, 2012, How immunohistochemistry can help to identify renal tumors associated with SDHB syndrome, Mod Pathol, 249A, 1046

Cited by

Sorted by citations

Items 101–200 of 215

Related

See all

Metadata

Authors
Gill, A. J.
Affiliations
The University of Sydney (AU)
Corresponding author
Gill, Anthony J.
ORCID
Gill, Anthony J.
Venue
Pathology
Publisher
Elsevier BV
Published
2012-06
Volume
44
Issue
4
Pages
285-292
ISSN
0031-3025 (ISSN-L)
DOI
10.1097/pat.0b013e3283539932
OpenAlex
W2156718948
Cited by
215
References
46
Citations by year
2026: 9 · 2025: 15 · 2024: 11 · 2023: 13 · 2022: 15 · 2021: 22 · 2020: 14 · 2019: 11 · 2018: 16 · 2017: 21 · 2016: 17 · 2015: 19 · 2014: 18 · 2013: 11 · 2012: 3
FWCI
3.15
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Pathology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal Tumor Research and Treatment
Keywords
succinate dehydrogenase, SDHB, SDHA, SDHC, SDHD, pheochromocytoma, paraganglioma, gastrointestinal stromal tumor, renal carcinoma, Carney triad, germline mutations, immunohistochemistry, tumourigenesis, hereditary cancer
MeSH terms
Gastrointestinal Neoplasms, Genetic Testing, Humans, Membrane Proteins, Neoplasms, Neoplastic Syndromes, Hereditary, Paraganglioma, Pheochromocytoma, Succinate Dehydrogenase, Gene Expression Regulation, Neoplastic, Germ-Line Mutation, Genetic Predisposition to Disease, Protein Subunits, Mitochondrial Proteins, Gastrointestinal Stromal Tumors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review