TY - JOUR
T1 - Two somatic biallelic lesions within and near SMAD4 in a human breast cancer cell line
AU - Jakob, John
AU - Nagase, Satoru
AU - Gazdar, Adi
AU - Chien, Minchen
AU - Morozova, Irina
AU - Russo, James J.
AU - Nandula, Subhadra V.
AU - Murty, Vundavalli V.V.S.
AU - Li, Chi Ming
AU - Tycko, Benjamin
AU - Parsons, Ramon
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/4
Y1 - 2005/4
N2 - Loss of chromosome arm 18q is a common event in human pancreatic, colon, and breast cancers and is often interpreted as representing loss of one or more tumor-suppressor genes. In this article, we describe two novel biallelic deletions at chromosome band 18q21.1 in a recently characterized human breast cancer cell line, HCC-1428. One lesion deletes a fragment of approximately 300 kb between SMAD4 and DCC that encodes no known genes. The second lesion is an in-frame SMAD4 deletion (amino acids 49-51) that affects the level of SMAD4 protein but not the SMAD4 message. This change accelerates 26S proteasome-mediated degradation of both endogenous and exogenous mutant SMAD4. Examination of normal DNA from the same patient demonstrated that both lesions are somatic and associated with loss of both normal alleles. These data support the concept that two independent tumor-suppressor loci exist at chromosome segment 18q21.1, one at SMAD4 and the other potentially at an enhancer of DCC or an unrelated novel gene.
AB - Loss of chromosome arm 18q is a common event in human pancreatic, colon, and breast cancers and is often interpreted as representing loss of one or more tumor-suppressor genes. In this article, we describe two novel biallelic deletions at chromosome band 18q21.1 in a recently characterized human breast cancer cell line, HCC-1428. One lesion deletes a fragment of approximately 300 kb between SMAD4 and DCC that encodes no known genes. The second lesion is an in-frame SMAD4 deletion (amino acids 49-51) that affects the level of SMAD4 protein but not the SMAD4 message. This change accelerates 26S proteasome-mediated degradation of both endogenous and exogenous mutant SMAD4. Examination of normal DNA from the same patient demonstrated that both lesions are somatic and associated with loss of both normal alleles. These data support the concept that two independent tumor-suppressor loci exist at chromosome segment 18q21.1, one at SMAD4 and the other potentially at an enhancer of DCC or an unrelated novel gene.
UR - http://www.scopus.com/inward/record.url?scp=13944266766&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13944266766&partnerID=8YFLogxK
U2 - 10.1002/gcc.20142
DO - 10.1002/gcc.20142
M3 - Article
C2 - 15645498
AN - SCOPUS:13944266766
VL - 42
SP - 372
EP - 383
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
SN - 1045-2257
IS - 4
ER -