Pituitary adenocarcinoma

Summary

Pituitary adenocarcinoma (MONDO:0017582) is a disease with 1 cohort gene and 3 clinical trials. Top therapeutic interventions include ipilimumab and lutetium oxodotreotide lu-177.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 22
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

25 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.04	Europe	Validated
Lifetime Prevalence	1-9 / 1 000 000	0.87	Europe	Validated
Annual incidence	<1 / 1 000 000	0.026	Austria	Validated
Annual incidence	<1 / 1 000 000	0.041	Belgium	Validated
Annual incidence	<1 / 1 000 000	0.014	Bulgaria	Validated
Annual incidence	<1 / 1 000 000	0.037	Czech Republic	Validated
Annual incidence	<1 / 1 000 000	0.009	Estonia	Validated
Annual incidence	<1 / 1 000 000	0.019	Finland	Validated
Annual incidence	<1 / 1 000 000	0.033	Germany	Validated
Annual incidence	<1 / 1 000 000	0.099	Ireland	Validated
Annual incidence	<1 / 1 000 000	0.052	Italy	Validated
Annual incidence	<1 / 1 000 000	0.016	Latvia	Validated
Annual incidence	<1 / 1 000 000	0.025	Lithuania	Validated
Annual incidence	<1 / 1 000 000	0.063	Malta	Validated
Annual incidence	<1 / 1 000 000	0.025	Norway	Validated
Annual incidence	<1 / 1 000 000	0.008	Portugal	Validated
Annual incidence	<1 / 1 000 000	0.021	Slovakia	Validated
Annual incidence	<1 / 1 000 000	0.006	Slovenia	Validated
Annual incidence	<1 / 1 000 000	0.021	Spain	Validated
Annual incidence	<1 / 1 000 000	0.006	Switzerland	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0011763	Pituitary carcinoma	Obligate (100%)
HP:0000870	Increased circulating prolactin concentration	Very frequent (80-99%)
HP:0002315	Headache	Very frequent (80-99%)
HP:0003154	Increased circulating ACTH level	Very frequent (80-99%)
HP:0006767	Pituitary prolactin cell adenoma	Very frequent (80-99%)
HP:0008291	Pituitary corticotropic cell adenoma	Very frequent (80-99%)
HP:0100836	Malignant neoplasm of the central nervous system	Very frequent (80-99%)
HP:0007663	Reduced visual acuity	Frequent (30-79%)
HP:0007987	Progressive visual field defects	Frequent (30-79%)
HP:0012377	Hemianopia	Frequent (30-79%)
HP:0012505	Enlarged pituitary gland	Frequent (30-79%)
HP:0040075	Hypopituitarism	Frequent (30-79%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000845	Elevated circulating growth hormone concentration	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0010514	Hyperpituitarism	Occasional (5-29%)
HP:0011442	Abnormality of central motor function	Occasional (5-29%)
HP:0011760	Pituitary growth hormone cell adenoma	Occasional (5-29%)
HP:0100561	Spinal cord lesion	Occasional (5-29%)
HP:0000873	Diabetes insipidus	Very rare (<1-4%)
HP:0011759	Pituitary gonadotropic cell adenoma	Very rare (<1-4%)
HP:0011762	Pituitary thyrotropic cell adenoma	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	pituitary adenocarcinoma
Mondo ID	MONDO:0017582
Orphanet	300385
DOID	DOID:4916
NCIT	C4536
SNOMED CT	254955001
UMLS	C0346300
MedGen	91096
GARD	0009371
Anatomy (UBERON)	UBERON:0000007
Is cancer (heuristic)	no

Also known as: cancer of pituitary · cancer of pituitary gland · cancer of the pituitary · cancer of the pituitary gland · carcinoma of pituitary · carcinoma of pituitary gland · carcinoma of the pituitary · carcinoma of the pituitary gland · pituitary adenocarcinoma (disease) · pituitary carcinoma · pituitary gland adenocarcinoma · pituitary gland cancer · pituitary gland carcinoma · PTCA

Data availability: 1 ClinVar variant · 1 HPO phenotype · 1 cell line.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › head and neck carcinoma › pituitary adenocarcinoma

Related subtypes (15): eye carcinoma, external ear carcinoma, middle ear carcinoma, nasal cavity carcinoma, growth hormone-producing pituitary gland carcinoma, hypopharyngeal carcinoma, ameloblastic carcinoma, laryngeal small cell carcinoma, pharyngeal adenoid cystic carcinoma, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, carcinoma of floor of mouth, lip and oral cavity carcinoma, oropharyngeal carcinoma, nasal cavity and paranasal sinus carcinoma

Subtypes (3): pituitary gland basophilic carcinoma, ACTH-producing pituitary gland carcinoma, prolactin-producing pituitary gland carcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
9245	NM_000535.7(PMS2):c.137G>T (p.Ser46Ile)	PMS2	Likely pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PMS2	Orphanet:144	Lynch syndrome
PMS2	Orphanet:252202	Constitutional mismatch repair deficiency syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
prefrontal cortex	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PMS2	143	ubiquitous	marker	thymus, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PMS2	2,658

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PMS2	P54278	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective Mismatch Repair Associated With MLH1	1	5710.0×	4e-04	PMS2
Defective Mismatch Repair Associated With PMS2	1	5710.0×	4e-04	PMS2
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	1	815.7×	0.002	PMS2
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	1	815.7×	0.002	PMS2
TP53 Regulates Transcription of DNA Repair Genes	1	181.3×	0.006	PMS2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
somatic recombination of immunoglobulin gene segments	1	4213.0×	0.001	PMS2
positive regulation of isotype switching to IgA isotypes	1	2808.7×	0.001	PMS2
positive regulation of isotype switching to IgG isotypes	1	1532.0×	0.001	PMS2
somatic hypermutation of immunoglobulin genes	1	1053.2×	0.001	PMS2
mismatch repair	1	648.1×	0.002	PMS2
response to xenobiotic stimulus	1	69.1×	0.014	PMS2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PMS2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PMS2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PMS2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PMS2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	2
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04042753	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab in People With Aggressive Pituitary Tumors
NCT04106843	PHASE2	WITHDRAWN	Radioactive Drug (177Lu-DOTATATE) for the Treatment of Locally Advanced, Metastatic, or Unresectable Rare Endocrine Cancers
NCT03507361	Not specified	UNKNOWN	Myocardial Damage and Music Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IPILIMUMAB	4	1
LUTETIUM OXODOTREOTIDE LU-177	4	1