Two somatic biallelic lesions within and near SMAD4 in a human breast cancer cell line

John Jakob, Satoru Nagase, Adi Gazdar, Minchen Chien, Irina Morozova, James J. Russo, Subhadra V. Nandula, Vundavalli V V S Murty, Chi Ming Li, Benjamin Tycko, Ramon Parsons

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)372-383
Number of pages12
JournalGenes Chromosomes and Cancer
Volume42
Issue number4
DOIs
StatePublished - Apr 2005

Fingerprint

Chromosomes
Breast Neoplasms
Cell Line
Chromosome Deletion
Tumor Suppressor Genes
Pancreatic Neoplasms
Colonic Neoplasms
Genes
Alleles
Amino Acids
DNA
Neoplasms
Proteins
ATP dependent 26S protease

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Jakob, J., Nagase, S., Gazdar, A., Chien, M., Morozova, I., Russo, J. J., ... Parsons, R. (2005). Two somatic biallelic lesions within and near SMAD4 in a human breast cancer cell line. Genes Chromosomes and Cancer, 42(4), 372-383. https://doi.org/10.1002/gcc.20142

Two somatic biallelic lesions within and near SMAD4 in a human breast cancer cell line. / Jakob, John; Nagase, Satoru; Gazdar, Adi; Chien, Minchen; Morozova, Irina; Russo, James J.; Nandula, Subhadra V.; Murty, Vundavalli V V S; Li, Chi Ming; Tycko, Benjamin; Parsons, Ramon.

In: Genes Chromosomes and Cancer, Vol. 42, No. 4, 04.2005, p. 372-383.

Research output: Contribution to journalArticle

Jakob, J, Nagase, S, Gazdar, A, Chien, M, Morozova, I, Russo, JJ, Nandula, SV, Murty, VVVS, Li, CM, Tycko, B & Parsons, R 2005, 'Two somatic biallelic lesions within and near SMAD4 in a human breast cancer cell line', Genes Chromosomes and Cancer, vol. 42, no. 4, pp. 372-383. https://doi.org/10.1002/gcc.20142
Jakob, John ; Nagase, Satoru ; Gazdar, Adi ; Chien, Minchen ; Morozova, Irina ; Russo, James J. ; Nandula, Subhadra V. ; Murty, Vundavalli V V S ; Li, Chi Ming ; Tycko, Benjamin ; Parsons, Ramon. / Two somatic biallelic lesions within and near SMAD4 in a human breast cancer cell line. In: Genes Chromosomes and Cancer. 2005 ; Vol. 42, No. 4. pp. 372-383.
@article{10742dd81f944401b854724c45f3497c,
title = "Two somatic biallelic lesions within and near SMAD4 in a human breast cancer cell line",
abstract = "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.",
author = "John Jakob and Satoru Nagase and Adi Gazdar and Minchen Chien and Irina Morozova and Russo, {James J.} and Nandula, {Subhadra V.} and Murty, {Vundavalli V V S} and Li, {Chi Ming} and Benjamin Tycko and Ramon Parsons",
year = "2005",
month = "4",
doi = "10.1002/gcc.20142",
language = "English (US)",
volume = "42",
pages = "372--383",
journal = "Genes Chromosomes and Cancer",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "4",

}

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

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 -