CDH1
In
databases :
HGNC (http://www.genenames.org/): 1748 or CDH1
Gene locus:
16q22.1
Protein name:
Cadherin 1, type 1, E-cadherin
(epithelial)
Protein Size:
882 amino acids; about 97 kDa
Function:
One of the most important and ubiquitous
types of adhesive interactions required for the maintenance of solid tissues is
that mediated by the classic cadherin adhesion molecules. Cadherins are
transmembrane Ca2+- dependent homophilic adhesion receptors that are well known
to play important roles in cell recognition and cell sorting during
development. However, they continue to be expressed at high levels in virtually
all solid tissues. There are many members of the classic cadherin family (which
is a subset of the larger cadherin superfamily), but E-cadherin in epithelial
tissues has been the most studied in the context of stable adhesions. Continued
expression and functional activity of E-cadherin are required for cells to
remain tightly associated in the epithelium, and in its absence the many other
cell adhesion and cell junction proteins expressed in epithelial cells (see
below) are not capable of supporting intercellular adhesion. In its capacity to
maintain the overall state of adhesion between epithelial cells, E-cadherin is
thought to act as an important suppressor of epithelial tumor cell invasiveness
and metastasis.
Cancer-related alterations:
Mutations in this gene are correlated with
gastric, breast, biliary tract, colorectal, thyroid and ovarian cancer.
Defects in CDH1 are a cause of hereditary
familial diffuse gastric cancer (HDGC). Dozens of CDH1 germline mutations have
been described in HDGC families. Most are inactivating (frameshift, nonsense,
and splice-site), the remainders are “missense”. The mutations are distributed
equally throughout the gene.
Somatic mutations in CDH1 were found in
about 56% of lobular breast tumors, generally (>90%) in combination with
loss of the wild-type allele, while no mutations were found in ductal primary
breast carcinomas. Most of these somatic mutations result in premature stop
codons as a consequence of insertions, deletions and nonsense mutations leading
to the loss of the CDH1 cell-cell adhesion functionality. Other cancer-confined
E-cadherin mutations also result in crippled proteins. The distinctive invasive
growth pattern, which is typical for lobular breast cancers, is fully
compatible with this functional inactivation.
Frequent somatic mutations (50%) in CDH have
been identified in sporadic diffuse gastric cancer (DGC). Most mutations are “missense”
(exons 8, 9) or exon skipping. In most cases, CDH1 mutations are found in
combination with loss of the wild-type allele.
References (open access):
Pathology of hereditary breast cancer. van der Groep P, van der Wall E,
van Diest PJ. Cell Oncol (Dordr). 2011 Apr;34(2):71-88.
Hereditary diffuse gastric cancer: prophylactic surgical oncology
implications. Lynch HT, Silva E, Wirtzfeld D, Hebbard P, Lynch J, Huntsman DG. Surg
Clin North Am. 2008 Aug;88(4):759-78, vi-vii.
Germline mutations in CDH1 are infrequent in women with early-onset or
familial lobular breast cancers. Schrader KA, Masciari S, Boyd N, Salamanca C,
Senz J, Saunders DN, Yorida E, Maines-Bandiera S, Kaurah P, Tung N, Robson ME,
Ryan PD, Olopade OI, Domchek SM, Ford J, Isaacs C, Brown P, Balmana J, Razzak
AR, Miron P, Coffey K, Terry MB, John EM, Andrulis IL, Knight JA, O'Malley FP,
Daly M, Bender P; kConFab, Moore R, Southey MC, Hopper JL, Garber JE, Huntsman
DG. J Med Genet. 2011 Jan;48(1):64-8.
E-cadherin polymorphisms and breast cancer susceptibility: a report from
the Shanghai
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