Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (56)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Guanti, G.
Right arrow Articles by Gentile, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guanti, G.
Right arrow Articles by Gentile, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2000, Vol. 9, No. 2 283-287
© 2000 Oxford University Press

Involvement of PTEN mutations in the genetic pathways of colorectal cancerogenesis

Ginevra Guanti+,§, Nicoletta Resta+, Cristiano Simone, Filomena Cariola1, Ignazio Demma2, Paola Fiorente1 and Mattia Gentile1

Dipartimento di Medicina Interna e Medicina Pubblica, Sezione di Genetica Medica, Policlinico, Piazza Giulio Cesare, 70124 Bari, Italy, 1Genetica Medica and 2Divisione di Chirurgia, IRCCS ‘De Bellis’, 70013 Castellana, Italy

So far, somatic mutations of the PTEN gene have been found in several different neoplasms but not in colorectal tumours. As exons 7 and 8 of the PTEN coding sequence contain an (A)6 repeat and mononucleotide repeat sequences are targets for mutations in tumours with microsatellite instability (MI), we screened a panel of sporadic colorectal tumours exhibiting MI to test whether PTEN gene repeats are frequently mutated in MI+ colorectal cancers. Of 32 cases studied, seven mutations were found in six (18.75%) patients, as a PTEN biallelic frameshift mutation was observed in one case, with consequent loss of function of the gene. Loss of heterozygosity, evaluated in the remaining five cases using the microsatellite marker D10S541, was detected in two of three informative samples. To further address the role of the PTEN gene in MI+ colorectal cancer, in the six patients with mutated PTEN, we analysed the mononucleotide repeats of six other genes: BAX, hMSH3, hMSH6, TGFbRII, IGFIIR and APC. In two of these six patients, mutations of the TGFbRII gene only were present, indicating that PTEN may have a role in the mutator pathway of colorectal tumorigenesis. Overall, these results indicate that PTEN mutations are selected for during tumorigenesis in MI+ colorectal tumours. The mutation of both PTEN alleles and evidence that the PTEN protein is expressed in normal colon suggest that loss of function of this gene could play a direct role in tumorigenesis.

+ These authors contributed equally to this work

§ To whom correspondence should be addressed. Tel: +39 0805478270; Fax: +39 0805478269; Email: guanti@medgene.uniba.it


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
P. Laurent-Puig, A. Lievre, and H. Blons
Mutations and Response to Epidermal Growth Factor Receptor Inhibitors
Clin. Cancer Res., February 15, 2009; 15(4): 1133 - 1139.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
A.H.S. Gylling, T.T. Nieminen, W.M. Abdel-Rahman, K. Nuorva, M. Juhola, E.I. Joensuu, H.J. Jarvinen, J.-P. Mecklin, M. Aarnio, and P.T. Peltomaki
Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors
Carcinogenesis, July 1, 2008; 29(7): 1351 - 1359.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Jhawer, S. Goel, A. J. Wilson, C. Montagna, Y.-H. Ling, D.-S. Byun, S. Nasser, D. Arango, J. Shin, L. Klampfer, et al.
PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab
Cancer Res., March 15, 2008; 68(6): 1953 - 1961.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. Li, S. J. Plummer, C. L. Thompson, T. C. Tucker, and G. Casey
Association between Phosphatidylinositol 3-Kinase Regulatory Subunit p85{alpha} Met326Ile Genetic Polymorphism and Colon Cancer Risk
Clin. Cancer Res., February 1, 2008; 14(3): 633 - 637.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Goel, C. N. Arnold, D. Niedzwiecki, J. M. Carethers, J. M. Dowell, L. Wasserman, C. Compton, R. J. Mayer, M. M. Bertagnolli, and C. R. Boland
Frequent Inactivation of PTEN by Promoter Hypermethylation in Microsatellite Instability-High Sporadic Colorectal Cancers
Cancer Res., May 1, 2004; 64(9): 3014 - 3021.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Ionov, S.-I. Matsui, and J. K. Cowell
A role for p300/CREB binding protein genes in promoting cancer progression in colon cancer cell lines with microsatellite instability
PNAS, February 3, 2004; 101(5): 1273 - 1278.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
J. M. Garcia, R. Rodriguez, J. Silva, C. Munoz, G. Dominguez, J. M. Silva, E. Carcereny, M. Provencio, P. Espana, and F. Bonilla
Intratumoral Heterogeneity in Microsatellite Alterations in BRCA1 and PTEN Regions in Sporadic Colorectal Cancer
Ann. Surg. Oncol., October 1, 2003; 10(8): 876 - 881.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
T. Kumagai, J. O'Kelly, J. W. Said, and H. P. Koeffler
Vitamin D2 Analog 19-nor-1,25-Dihydroxyvitamin D2: Antitumor Activity Against Leukemia, Myeloma, and Colon Cancer Cells
J Natl Cancer Inst, June 18, 2003; 95(12): 896 - 905.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
S Vilkki, V Launonen, A Karhu, P Sistonen, I Vastrik, and L A Aaltonen
Screening for microsatellite instability target genes in colorectal cancers
J. Med. Genet., November 1, 2002; 39(11): 785 - 789.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
X.-P. Zhou, A. Loukola, R. Salovaara, M. Nystrom-Lahti, P. Peltomaki, A. de la Chapelle, L. A. Aaltonen, and C. Eng
PTEN Mutational Spectra, Expression Levels, and Subcellular Localization in Microsatellite Stable and Unstable Colorectal Cancers
Am. J. Pathol., August 1, 2002; 161(2): 439 - 447.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. A. Kuismanen, A.-L. Moisio, P. Schweizer, K. Truninger, R. Salovaara, J. Arola, R. Butzow, J. Jiricny, M. Nystrom-Lahti, and P. Peltomaki
Endometrial and Colorectal Tumors from Patients with Hereditary Nonpolyposis Colon Cancer Display Different Patterns of Microsatellite Instability
Am. J. Pathol., June 1, 2002; 160(6): 1953 - 1958.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Duval and R. Hamelin
Mutations at Coding Repeat Sequences in Mismatch Repair-deficient Human Cancers: Toward a New Concept of Target Genes for Instability
Cancer Res., May 1, 2002; 62(9): 2447 - 2454.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
X.-P. Zhou, S. Kuismanen, M. Nystrom-Lahti, P. Peltomaki, and C. Eng
Distinct PTEN mutational spectra in hereditary non-polyposis colon cancer syndrome-related endometrial carcinomas compared to sporadic microsatellite unstable tumors
Hum. Mol. Genet., February 1, 2002; 11(4): 445 - 450.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Dicuonzo, S. Angeletti, J. Garcia-Foncillas, A. Brugarolas, Y. Okrouzhnov, D. Santini, G. Tonini, G. Lorino, M. De Cesaris, and A. Baldi
Colorectal Carcinomas and PTEN/MMAC1 Gene Mutations
Clin. Cancer Res., December 1, 2001; 7(12): 4049 - 4053.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. Peltomaki
Deficient DNA mismatch repair: a common etiologic factor for colon cancer
Hum. Mol. Genet., April 1, 2001; 10(7): 735 - 740.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Yamamoto, F. Itoh, H. Nakamura, H. Fukushima, S. Sasaki, M. Perucho, and K. Imai
Genetic and Clinical Features of Human Pancreatic Ductal Adenocarcinomas with Widespread Microsatellite Instability
Cancer Res., April 1, 2001; 61(7): 3139 - 3144.
[Abstract] [Full Text]

Home page
 Hum Mol GenetHome page
A. Duval, S. Rolland, A. Compoint, E. Tubacher, B. Iacopetta, G. Thomas, and R. Hamelin
Evolution of instability at coding and non-coding repeat sequences in human MSI-H colorectal cancers
Hum. Mol. Genet., March 1, 2001; 10(5): 513 - 518.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
O. Gimm, T. Attie-Bitach, J. A. Lees, M. Vekemans, and C. Eng
Expression of the PTEN tumour suppressor protein during human development
Hum. Mol. Genet., July 1, 2000; 9(11): 1633 - 1639.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Arico, A. Petiot, C. Bauvy, P. F. Dubbelhuis, A. J. Meijer, P. Codogno, and E. Ogier-Denis
The Tumor Suppressor PTEN Positively Regulates Macroautophagy by Inhibiting the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway
J. Biol. Chem., September 14, 2001; 276(38): 35243 - 35246.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.