tumor predisposition syndromes

Cancer predisposition are related to anomalies of DNA metabolism, DNA repair, cell-cycle governance, or control of apoptosis.

Classification

 anomalies of DNA metabolism

• rhabdoid tumor predisposition syndrome (INI1)

 dysregulation of telomere shortening

• dyskeratosis congenita (DKC)

 DNA repair anomalies

• DNA mismatch repair anomalies (HNPCC)
• base excision repair anomalies (BER)
• ataxia telangiectasia (ATM)

• DNA helicases mutations
  • Bloom syndrome : mutations in the DNA helicase RecQ protein-like-3 (MIM.604610)
  • Cockayne syndrome
  • Diamond-Blackfan anemia (DBA)
  • Fanconi disease (Fanconi syndrome or Fanconi anemia)
  • Xeroderma pigmentosum
  • trichothiodystrophy (TTD)
  • Werner syndrome

 DNA checkpoint anomalies

• Li-Fraumeni syndrome (TP53)

 cell-cycle governance

• retinoblastoma predisposition (RB)

 control of apoptosis

 growth signal signal transduction

• transmembrane receptors
  • Bannayan-Riley-Ruvalcaba syndrome
  • Cowden Disease

• cytoplasmic proteins
  • Costello syndrome (HRAS)

• transcription factors
  • WT1-associated diseases (WT1)
    • Denys-Drash syndrome (WT1)
    • WAGR (Wilms tumor/aniridia/genitourinary anomalies/mental retardation syndrome) (11p13 deletion)

 methylation control

• Beckwith-Wiedemann syndrome (11p15.5)

 adhesion proteins

• familial gastric carcinoma (CDN1 mutations)

To class

 Bruton agammaglobulinemia
 Carney complex
 congenital neutropenia
 diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)
 Dubowitz syndrome
 dysplastic nevus syndrome (DNS)
 epidermodysplasia verruciformis
 familial /sporadic gastrointestinal stromal tumors (GISTs)
 familial chronic lymphocytic leukaemia
 familial gastric carcinoma (CDN1 mutations)
 familial monosomy 7 syndrome
 familial adenomatous polyposis (FAP)
 familial nervous system tumour syndromes
 hereditary pancreatic carcinoma
 hereditary paraganglioma (PGL)
 hereditary breast cancer
 hereditary multiple exostoses (HME)
 hereditary non polyposis colorectal carcinoma (HNPCC Syndrome)
 hereditary papillary renal cell carcinoma
 hyperparathyroidism-jaw tumor syndrome (HPT-JT)
 Lhermitte-Duclos disease
 multiple Endocrine Neoplasia type 1 (MEN1)
 multiple Endocrine Neoplasia type 2 (MEN2)
 naevoid basal cell carcinoma syndrome (NBCS)
 neurofibromatosis type 1 (NF1)
 neurofibromatosis type 2 (NF2)
 Nijmegen breakage syndrome
 Peutz-Jeghers syndrome
 piebaldism
 Rothmund-Thomson syndrome (RTS)
 Rubinstein-Taybi syndrome (RTS)
 Simpson-Golabi-Behmel syndrome
 Sotos syndrome
 Sturge-Weber syndrome
 tuberous sclerosis (TSC)
 variegated aneuploidy related to premature centromere division (PCD)
 Von Hippel-Lindau disease (VHL)

 metabolic enzymes anomalies

• cutaneous and uterine leiomyomatosis(MIM.150800): mutations in fumarate hydratase (FH) or fumarase
• hereditary leiomyomatosis and renal cell cancer syndrome (MIM.605839): mutations in fumarate hydratase (FH) or fumarase
• predisposition to paraganglioma: mutations in three of the succinate dehydrogenase (SDH, mitochondrial complex II) subunits (SDHD, SDHB and SDHC)

 chromosomal diseases

• Down syndrome
• constitutional trisomy 8 mosaicism (8616798, 8913726)
• Turner syndrome
• Klinefelter syndrome

Diseases by alphabetic orders

ataxia telangiectasia	ATM	11q22.3
Bannayan-Ruvalcaba-Riley syndrome	PTEN	10q23.31
Beckwith-Wiedemann syndrome	-	11p15.5
Birt-Hogg-Dube syndrome	FLCN	17p11.2
Bloom syndrome	RECQL3	15q26.1
Bruton agammaglobulinemia	BTK	Xq21.3-q22
Carney complex 1	PRKAR1A	17q23-q24
Carney complex 2	-	2p16
Carney triad	-	-
Cockayne syndrome A	ERCC8	5q11
Cockayne syndrome B	ERCC6	10q11
Cockayne syndrome C	-	-
severe congenital neutropenia 1	ELA2	19p13.3
severe congenital neutropenia 2	GFI1	1p22
Costello syndrome	HRAS	11p15.5
Cowden disease	PTEN	10q23.31
Denys-Drash syndrome	WT1	11p13
Diamond-Blackfan anemia 1	RPS19	19q13.2
Diamond-Blackfan anemia 2	-	8p23.3-p22
diaphyseal medullary stenosis with MFH	-	9p22-p21
Dubowitz syndrome	-	-
dyskeratosis congenita autosomal dominant	TERC	3q21-q28
dyskeratosis congenita X-linked	DKC1	Xq28
dyskeratosis congenita autosomal recessive	-	-
dysplastic nevus syndrome	-	-
epidermodysplasia verruciformis 1	EVER1	17q25
epidermodysplasia verruciformis 2	EVER2	17q25
familial GISTs	KIT	4q12
familial chronic lymphocytic leukemia	-	-
familial cutaneous malignant melanoma 1 CMM1	-	1p36
familial cutaneous malignant melanoma 2 CMM2	CDKN2	9p21
familial cutaneous malignant melanoma 3 CMM3	CDK4	12q14
familial cutaneous malignant melanoma 4 CMM4	-	1p22
familial gastric carcinoma	CDH1	MIM.192090	16q22.1
familial monosomy 7 Syndrome
familial adenomatous polyposis	APC	5q22
familial nervous system tumour syndrome
familial neuroblastoma 1	PHOX2B	16p12-13
familial neuroblastoma 2	-	4p12
Fanconi syndrome (Fanconi anemia)
Fanconi anemia A (FANCA)	FANCA	16q24.3
Fanconi anemia B (FANCB)	FAAP95	Xp22.31
Fanconi anemia C (FANCC)	-	9q22.3
Fanconi anemia D1 (FANCD1)	BRCA2	13q12.3
Fanconi anemia D2 (FANCD2)	-	3p25.3
Fanconi anemia E (FANCE)	-	6p22-p21
Fanconi anemia F (FANCF)	-	11p15
Fanconi anemia G (FANCG)	-	9p13
hereditary pancreatic cancer	-	-
hereditary paraganglioma 1 (PGL1)	SDHD	11q23
hereditary paraganglioma 2 (PGL2)	-	11q13
hereditary paraganglioma 3 (PGL3)	SDHC	1q21
hereditary paraganglioma 4 (PGL4)	SDHB	1p36
hereditary breast cancer 1	BRCA1	-
hereditary breast cancer 2	BRCA2	-
hereditary multiple exostoses 1	EXT1	8q24
hereditary multiple exostoses 2	EXT2	11p12-p11
hereditary multiple exostoses 3	-	19p
hereditary non polyposis colorectal carcinoma - HNPCC
hereditary papillary renal cell carcinoma	MEt	7q31
hyperparathyroidism-jaw tumor syndrome -HPT-JT	1q25-q31	1q25-q31
juvenile polyposis syndrome	SMAD4	18q21.1
juvenile polyposis syndrome with HHT	SMAD4	18q21.1
leiomyomatosis and renal cell cancer	FH	1q42.1
leiomyomatosis of the skin	FH	1q42.1
Lhermitte-Duclos disease	PTEN	10q23.31
Li-Fraumeni syndrome	TP53	17p13.1
multiple Endocrine Neoplasia type 1	MEN1	11q13
multiple Endocrine Neoplasia type 2	RET	10q11.2
basal cell nevus syndrome 1 (BCNS1)	PTCH1	9q22.3
basal cell nevus syndrome 2 (BCNS2)	PTCH2	1p32
neurofibromatosis type 1	NF1	17q11.2
neurofibromatosis type 1	MLH1	3p21.3
neurofibromatosis type 1	MSH2	2p22-p21
neurofibromatosis type 2	NF2	22q12.2
Nijmegen breakage syndrome	NBS1	8q21
Peutz-Jeghers syndrome	STK11	19p13.3
piebaldism 1	KIT	4q11-q12
piebaldism 2	SNAI2	8q11
retinoblastoma	RB	13q14.1-q14.2
Rhabdoid predisposition syndrome	SMARCB1 (INI1/SNF5)	22q11
Rothmund-Thomson syndrome	RECQL4	8q24.3
Rubinstein-Taybi syndrome 1	CREBBP	16p13.3
Rubinstein-Taybi syndrome 2	EP300	22q13
Simpson-Golabi-Behmel syndrome 1 SGBS1	GPC3	Xq26
Simpson-Golabi-Behmel syndrome 2 SGBS2	-	Xp22
Sotos syndrome	XH2	Xq13
Sturge-Weber syndrome	-	-
trichothiodystrophy photosensitive 1 (TTDP1)	ERCC2	19q13.2-q13.3
trichothiodystrophy photosensitive 2 (TTDP2)	ERCC3	2q21
trichothiodystrophy non photosensitive	C7ORF11	7p14
tuberous sclerosis 1 (TSC1)	TSC1	9q34
tuberous sclerosis 2 (TSC2)	TSC2	16p13.3
tuberous sclerosis 3 (TSC3)	-	-
tuberous sclerosis 4 (TSC4)	-	-
variegated aneuploidy with premature centromere division	-	-
Von Hippel-Lindau disease	VHL	3p26-p25
WAGR syndrome	WT1	11p13
Werner syndrome typical	RECQL2	8p12-p11.2
Werner syndrome atypical	LMNA	1q21.2
Wilms tumor predispostion	WT1	11p13	xeroderma pigmentosum A	XPA	9q22.3
xeroderma pigmentosum B	ERCC3	2q21
xeroderma pigmentosum C	XPC	3p25
xeroderma pigmentosum D	ERCC2	19q13.2-q13.3
xeroderma pigmentosum E	DDB2	11p12-p11
xeroderma pigmentosum F	ERCC4	16p13.3-p13.13
xeroderma pigmentosum G	ERCC5	13q33
xeroderma pigmentosum H	-	-
xeroderma pigmentosum I	-	-

References

 Frank SA. Genetic predisposition to cancer - insights from population genetics. Nat Rev Genet. 2004 Oct;5(10):764-72. PMID: 15510167

 Lerman C, Shields AE. Genetic testing for cancer susceptibility: the promise and the pitfalls. Nat Rev Cancer. 2004 Mar;4(3):235-41. PMID: 14993905

 Demant P. Cancer susceptibility in the mouse: genetics, biology and implications for human cancer. Nat Rev Genet. 2003 Sep;4(9):721-34. PMID: 12951573

 Eng C, Kiuru M, Fernandez MJ, Aaltonen LA. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer. 2003 Mar;3(3):193-202.
PMID: 12612654