PMID- 18094375
OWN - NLM
STAT- MEDLINE
DCOM- 20071227
LR  - 20220318
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 357
IP  - 25
DP  - 2007 Dec 20
TI  - Breast-cancer stromal cells with TP53 mutations and nodal metastases.
PG  - 2543-51
AB  - BACKGROUND: The importance of cross-talk between a cancer and its 
      microenvironment has been increasingly recognized. We hypothesized that 
      mutational inactivation of the tumor-suppressor gene TP53 and genomic alterations 
      in stromal cells of a tumor's microenvironment contribute to the clinical 
      outcome. METHODS: We performed TP53 mutation analysis and genomewide analysis of 
      loss of heterozygosity and allelic imbalance on DNA from isolated neoplastic 
      epithelial and stromal cells from 43 patients with hereditary breast cancer and 
      175 patients with sporadic breast cancer. Compartment-specific patterns and TP53 
      mutations were analyzed. Associations between compartment-specific TP53 status, 
      loss of heterozygosity or allelic imbalance, and clinical and pathological 
      characteristics were computed. RESULTS: TP53 mutations were associated with an 
      increased loss of heterozygosity and allelic imbalance in both hereditary and 
      sporadic breast cancers, but samples from patients with hereditary disease had 
      more frequent mutations than did those from patients with sporadic tumors (74.4% 
      vs. 42.3%, P=0.001). Only 1 microsatellite locus (2p25.1) in stromal cells from 
      hereditary breast cancers was associated with mutated TP53, whereas there were 66 
      such loci in cells from sporadic breast cancers. Somatic TP53 mutations in 
      stroma, but not epithelium, of sporadic breast cancers were associated with 
      regional nodal metastases (P=0.003). A specific set of five loci linked to an 
      increased loss of heterozygosity and allelic imbalance in the stroma of sporadic 
      tumors was associated with nodal metastases in the absence of TP53 mutations. No 
      associations were found between any of the clinical or pathological features of 
      hereditary breast cancer with somatic TP53 mutations. CONCLUSIONS: 
      Stroma-specific loss of heterozygosity or allelic imbalance is associated with 
      somatic TP53 mutations and regional lymph-node metastases in sporadic breast 
      cancer but not in hereditary breast cancer.
CI  - Copyright 2007 Massachusetts Medical Society.
FAU - Patocs, Attila
AU  - Patocs A
AD  - Genomic Medicine Institute, Cleveland Clinic Foundation, Cleveland 44195, USA.
FAU - Zhang, Li
AU  - Zhang L
FAU - Xu, Yaomin
AU  - Xu Y
FAU - Weber, Frank
AU  - Weber F
FAU - Caldes, Trinidad
AU  - Caldes T
FAU - Mutter, George L
AU  - Mutter GL
FAU - Platzer, Petra
AU  - Platzer P
FAU - Eng, Charis
AU  - Eng C
LA  - eng
GR  - 1P01CA97189-01A2/CA/NCI NIH HHS/United States
GR  - 1P50/U54CA113001-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (DNA, Neoplasm)
SB  - IM
CIN - N Engl J Med. 2007 Dec 20;357(25):2537-8. PMID: 18094373
CIN - N Engl J Med. 2008 Apr 10;358(15):1634-5; author reply 1636. PMID: 18403774
CIN - N Engl J Med. 2008 Apr 10;358(15):1636; author reply 1636. PMID: 18411428
CIN - N Engl J Med. 2008 Apr 10;358(15):1635-6; author reply 1636. PMID: 18411429
CIN - N Engl J Med. 2008 Apr 10;358(15):1635; author reply 1636. PMID: 18411430
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Allelic Imbalance
MH  - Breast/cytology
MH  - Breast Neoplasms/*genetics/pathology
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/analysis
MH  - Female
MH  - *Genes, p53
MH  - Genetic Diseases, Inborn/genetics/pathology
MH  - Genotype
MH  - Humans
MH  - Loss of Heterozygosity
MH  - Lymphatic Metastasis/*genetics
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - *Mutation, Missense
MH  - Neoplasm Invasiveness
MH  - Polymerase Chain Reaction
MH  - Receptor Cross-Talk
MH  - *Stromal Cells
EDAT- 2007/12/21 09:00
MHDA- 2007/12/29 09:00
CRDT- 2007/12/21 09:00
PHST- 2007/12/21 09:00 [pubmed]
PHST- 2007/12/29 09:00 [medline]
PHST- 2007/12/21 09:00 [entrez]
AID - 357/25/2543 [pii]
AID - 10.1056/NEJMoa071825 [doi]
PST - ppublish
SO  - N Engl J Med. 2007 Dec 20;357(25):2543-51. doi: 10.1056/NEJMoa071825.