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Two somatic biallelic lesions within and near SMAD4 in a human breast cancer cell line
Author(s) -
Jakob John,
Nagase Satoru,
Gazdar Adi,
Chien Minchen,
Morozova Irina,
Russo James J.,
Nandula Subhadra V.,
Murty Vundavalli V. V. S.,
Li ChiMing,
Tycko Benjamin,
Parsons Ramon
Publication year - 2005
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20142
Subject(s) - biology , somatic cell , gene , tumor suppressor gene , loss of heterozygosity , genetics , allele , cancer , chromosome , cancer research , deleted in colorectal cancer , mutation , breast cancer , carcinogenesis , colorectal cancer
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. © 2005 Wiley‐Liss, Inc.