RT Book, Section
A1 Eng, Charis
A1 Parsons, Ramon
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181416126
T1 Cowden Syndrome
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181416126
RD 2024/04/20
AB Cowden  syndrome  (CS)  is  an  autosomal  dominant  disorder  characterized  by  multiple  hamartomas  and  a  risk  of  breast  and  thyroid  cancers.The  great  majority  of  tumors,  including  those  of  the  thyroid  and  breast,  are  benign.  Up  to  10  percent  of  affected  individuals  develop  nonmedullary  thyroid  carcinoma,  and  up  to  50  percent  of  affected  females  develop  breast  cancer.The  pathognomonic  hamartoma  is  the  trichilemmoma,  a  benign  tumor  of  the  infundibulum  of  the  hair  follicle.The  susceptibility  gene  for  CS  is  a  tumor-suppressor  gene  as  evidenced  by  loss  of  heterozygosity  in  the  PTEN  region  of  10q23  in  various  tumors  and  by  transfection.The  CS  gene  PTEN  was  isolated  by  a  combination  of  genetic  mapping  analyses,  somatic  genetics,  and  a  candidate  gene  approach.  PTEN,  located  on  10q23.3,  encodes  a  403-amino  acid  protein,  which  contains  a  phosphatase  signature  motif  and  has  sequences  homologous  to  tensin.PTEN  is  a  dual-specificity  lipid  phosphatase.  PTEN  is  the  3-phosphatase  for  phosphotidylinositol-3,4,5-triphosphate  and,  hence,  coordinately  regulates  the  cell  survival  factor  PKB/Akt  via  the  PI3  kinase  signaling  pathway.Germ  line  mutations  in  PTEN  have  been  found  in  CS  families  as  well  as  in  the  related  but  distinct  hamartoma  disorder  Bannayan-Ruvalcaba-Riley  syndrome.  These  mutations  result  in  predicted  protein  truncation  or  likely  loss  of  function,  hence  supporting  its  predicted  function  as  a  tumor  suppressor.Somatic  mutations  of  PTEN  occur  in  a  broad  spectrum  of  sporadic  tumors,  which  is  almost  always  biallelic.  However,  alternate  mechanisms  of  PTEN  inactivation  do  occur.