Table 1.
Familial cancer syndromes involving the head and neck: genetic
| Disease/phenotype | Inheritance | Locus | Gene(s) | Encoded protein(s) | Normal protein function |
|---|---|---|---|---|---|
| Naevoid basal cell carcinoma syndrome: | |||||
| Naevoid basal cell carcinoma syndrome 1 | AD | 9q22.3 | PTCH1 | PTCH1 | Plays a role in embryonic development and regulates hedgehog signalling |
| Naevoid basal cell carcinoma syndrome 2 | AD | 10q24.3 | SUFU | SUFU | Inhibits hedgehog signalling |
| Neurofibromatosis 1 (NF1) | AD | 17q11 | NF1 | Neurofibromin (NF1) | Regulation of RAS signalling |
| Familial adenomatous polyposis with the Gardner syndrome variant | AD | 5q22.2 | APC | APC | Negative regulation of β-catenin and WNT signalling |
| Brooke-Spiegler syndrome | AD | 16q12.1 | CYLD | CYLD | Negatively regulates NF-κB activation |
| PTEN hamartoma tumor syndrome/Cowden syndrome: | |||||
| Cowden syndrome 1 | AD | 10q23.31 | PTEN | PTEN | A phosphatase; regulation of cell division (tumour suppressor) |
| Cowden syndrome 4 | AD | 10q23.31 | KLLN | Killin | Triggers apoptosis |
| Cowden syndrome 5 | AD | 3q26.32 | PIK3CA | PIK3CA (p110) | A catalytic subunit of PI3K |
| Cowden syndrome 6 | AD | 14q32.33 | AKT1 | AKT1 | Modulation of the AKT/mTOR signalling pathway |
| Cowden syndrome 7 | AD | 20p11.23 | SEC23B | SEC23B | ER-associated protein secretion |
| Hereditary paraganglioma syndromes: | |||||
| -SDH-deficient: | Dysfunction of the SDH complex enzyme involved in a broad spectrum of tumorigenic pathways including hypoxic regulation | ||||
| PGL1 | AD; PT | 11q23.1 | SDHD | SDHD | |
| PGL2 | AD; PT | 11q12.2 | SDHAF2 | SDHAF2 | |
| PGL3 | AD | 1q23.3 | SDHC | SDHC | |
| PGL4 | AD | 1p36.1-p35 | SDHB | SDHB | |
| PGL5 | AD | 5p15 | SDHA | SDHA | |
| -MEN2 | AD | 10q11.21 | RET | RET | Normal development of nerve cells |
| -VHL | AD | 3p25.3 | VHL | VHL | Ubiquitination and degradation of HIF (tumour suppressor) |
| -NF1 | AD | 17q11 | NF1 | Neurofibromin (NF1) | Regulation of RAS signalling |
| -Other genes: | |||||
| MAX; TMEM127; FH; KIF1B; EGLN1,2,3; EPAS1; MEN1 | |||||
| Multiple endocrine neoplasia type 2B | AD | 10q11.21 | RET | RET | Normal development of nerve cells |
| Hyperparathyroidism-Jaw tumour syndrome | AD | 1q25-q31 | CDC73 | Parafibromin | Parafibromin is a critical component of the PAF1C that binds to RNA polymerase II and controls transcription |
| Li–Fraumeni syndrome, TP53-associated | AD | 17p13.1 | TP53 | p53 | Regulation of cell division (tumour suppressor) |
| Li–Fraumeni syndrome, CHEK2-associated | AD | 22q12.1 | CHEK2 | CHEK2 | Induction of cell-cycle arrest and apoptosis after DNA damage |
| Fanconi anemia | Most AR FANC-Bis: X-linked and FANC-R: AD | 16q24.3 | FANCA (FA1) | FANCA | Some are involved in the repair of DNA damage |
| Dyskeratosis congenita | Most X-linked, AD, AR | 3q26.2 | DKCA | DKCA | Defective telomere maintenance caused by germline mutations in genes important in telomere biology |
| Ataxia telangiectasia syndrome | AR | 11q22.3 | ATM | ATM | Absence of ATM protein affects genomic instability or DNA damage response, leading to the development of tumours |
| Bloom syndrome | AR | 15q26.1 | BLM | BLM | BLM protein normally suppresses hyperrecombination |
| VonHippel Lindau syndrome | AD | 3p25.3 | VHL | VHL | Ubiquitination and degradation of HIF (tumour suppressor) |
| Tuberous sclerosis syndrome | |||||
| Tuberous sclerosis type 1 | AD | 9q34 | TSC1 | Hamartin | Interacts with tuberin; inhibits growth |
| Tuberous sclerosis type 2 | AD | 16p13.3 | TSC2 | Tuberin | Interacts with hamartin; inhibits growth |