Copyright ©The Author(s) 2015.
World J Gastrointest Oncol. Nov 15, 2015; 7(11): 347-355
Published online Nov 15, 2015. doi: 10.4251/wjgo.v7.i11.347
Table 1 The molecular profile and geographic particularities of inherited gastrointestinal cancer-predisposing syndromes[1-36]
Name of the syndromeMutated genesType of mutationGeographic particularities
FAPAPC: Exon 15 - first half (54% of patients with FAP)Classic phenotype: mutations between codons 178 and 309, and between 409 and 1580 (exons 5-8 and 9-14)NS
Germline truncation (C > T), especially at codons 1309 and 1061:
Nonsense mutations (28%)
Small insertions (10%)
Small deletions (46%)
APC: Chromosome arms 5q, 8p, 17p and 18qLOHNS
β-catenin: Exon 3 (15%)NSNS
APC/β-catenin (28%)NSNS
K-ras: Codon 12 (3%) - associated mutationGGT to TGT/GTTNS
Gardner syndromeAPC: Long arm of chromosome 5Interstitial deletionNS
APC: Patients with congenital hypertrophy of the retinal pigment epitheliumTruncating mutations between codons 311 and 1465NS
APC: Patients with desmoid tumorDownstream codon 1400 (1445-2011)NS
APC: Patients with gastro-duodenal adenomasMutations at the 3’ before codon 1395 and between codons 564 and 1493NS
APC: Patients with hepatoblastomasMutations at the 5’ to the mid region between codons 141 and 1751NS
APC: Patients with thyroid tumorsMutations between codons 140 and 1309NS
APC: Exons 3 and 4 (5’ end of the gene), exon 9, and the very 3’ end of the gene beyond codon 1595Truncating mutationNS
APC: VariantsMissense mutations I1307 K N1026S E1317QI1307K: almost exclusively in Ashkenazi Jewish descendents - detected in 6% of all family members, with 10%-20% lifetime risk of developing CRC
N1026S: Identified in one Spanish AFAP family (all members)
E1317Q: NS
MUTYH-associated polyposisMUTYH: Located on the chromosome 1p34.3-p32.1, contains 16 exonsGermline biallelic inactivationAbsent in Asia (Japan, Taiwan, South Korea)
Missense mutations: p.Y179C - exon 7 (c.536A > G; p.Tyr179Cys ) p.G396D - exon 13 (c.1187g > A;p.Gly396Asp)Specific for Eastern, Southern, and Central Europe, North America, European inhabitants from Canada, and Sephardi Jews Absent in Finland, India, Pakistan, Tunisia, Singapore, and Ashkenazi Jewish
Missense mutation p.Ala385ProfsX23Specific for Northern Europe
p.E410GfsX43Specific for Tunisia
Missense mutation p.Y104XSpecific for Pakistan
Missense mutation p.E480XSpecific for India
MUTYH variantsHeterozygous mutationsAsia (Japan, Taiwan, South Korea): p.Arg19; p.Arg109Trp; p.Gly286Glu
Southern Europe: p.Glu480del Pakistan: p.Tyr104 India: p.Glu480
K-ras: Codon 12 - associated mutation (64%), usually in patients with sessile serrated adenomasc.34G > TNS
Juvenile polyposis syndrome (pure type)MADH4/SMAD4/DPC4: Chromosome 18q21.1 (30%)NSNS
BMPR1A: Chromosome 10q23 (20%-30%)Large deletionsNS
Other genes (49%)NSNS
ENG: exons 11, 12
PTEN: chromosome 10q23.3
Juvenile polyposis + hemorrhagic telangiectasiaMADH4/SMAD4/DPC4: Chromosome 18q21.1 STK11: Chromosome 19p13.3 or 19q13.4 (50%-94%)NSNS NS
Peutz-Jeghers syndromeTGF-βPTEN: Chromosome 10q23.3NSNS
Peutz-Jeghers syndrome + primary pulmonary hypertensionALK1/ACVRL1NSNS
Cowden syndromePTEN: Chromosome 10q23.3 (13-85%)Nonsense mutations missense mutations frameshift mutations Large deletionsNS
Bannayan-Riley-Ruvalcaba syndromePTEN: Chromosome 10q23.3 (60%-65%)NSNS
Hereditary mixed polyposis syndromeBMPR1A: Chromosome 10q23NSNS
Li-Fraumeni syndrome – classic typep53: Exons 4-9 (23%-50%)NSNS
Unclassified/unexplained polyposis syndromes (50%)PTEN: Chromosome 10q23.3Nonsense mutations missense mutations frameshift mutationsNS
Other genes: BMPR2, ACRV1, SMAD1, SMAD2, SMAD3, SMAD5, SMAD7 (22%)NSNS