Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome

Debbie J. Marsh, Stina Roth, Kathryn L. Lunetta, Akseli Hemminki, Patricia L M Dahia, Pertti Sistonen, Zimu Zheng, Stacey Caron, Nathalie J. Van Orsouw, Walter F. Bodmer, Sally E. Cottrell, Malcolm G. Dunlop, Diana Eccles, Shirley V. Hodgson, Heikki Järvinen, Ilmo Kellokumpu, David Markie, Kay Neale, Robin Phillips, Paul RozenSapna Syngal, Jan Vijg, Ian P M Tomlinson, Lauri A. Aaltonen, Charis Eng

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Abstract

Juvenile polyposis syndrome (JPS; MIM 174900) is an autosomal dominant condition with incomplete penetrance characterized by hamartomatous polyps of the gastrointestinal tract and a risk of gastrointestinal cancer. Gastrointestinal hamartomatous polyps are also present in Cowden syndrome (CS; MIM 158350) and Bannayan-Zonana syndrome (BZS; also called Ruvalcaba- Myhre-Smith syndrome; MIM 153480). The susceptibility locus for both CS and BZS has recently been identified as the novel tumor suppressor gene PTEN, encoding a dual specificity phosphatase, located at 10q23.3. A putative JPS locus, JP1, which most likely functions as a tumor suppressor, bad previously been mapped to 10q22-24 in both familial and sporadic juvenile polyps. Given the shared clinical features of gastrointestinal hamartomatous polyps among the three syndromes and the coincident mopping of JP1 to the region of PTEN, we sought to determine whether JPS was allelic to CS and BZS by mutation analysis of PTEN and linkage approaches. Microsatellite markers spanning the CS/BZS locus (D10S219, D10S551, D10S579, and D10S541) were used to compute multipoint lod scores in eight informative families with JPS. lod scores of < -2.0 were generated for the entire region, thus excluding PTEN and any genes within the flanking 20-cM interval as candidate loci for familial JPS under our statistical models. In addition, analysis of PTEN using a combination of denaturing gradient gel electrophoresis and direct sequencing was unable to identify a germline mutation in 14 families with JPS and 11 sporadic cases. Therefore, at least a proportion of JPS cases are not caused by germline PTEN alteration or by an alternative locus at 10q22-24.

Original languageEnglish (US)
Pages (from-to)5017-5021
Number of pages5
JournalCancer Research
Volume57
Issue number22
StatePublished - Nov 15 1997
Externally publishedYes

Fingerprint

Multiple Hamartoma Syndrome
Polyps
Lod Score
Dual-Specificity Phosphatases
Denaturing Gradient Gel Electrophoresis
Gastrointestinal Neoplasms
Penetrance
Germ-Line Mutation
Statistical Models
Tumor Suppressor Genes
Microsatellite Repeats
Gastrointestinal Tract
Mutation
Juvenile polyposis syndrome
Genes
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Marsh, D. J., Roth, S., Lunetta, K. L., Hemminki, A., Dahia, P. L. M., Sistonen, P., ... Eng, C. (1997). Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome. Cancer Research, 57(22), 5017-5021.

Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome. / Marsh, Debbie J.; Roth, Stina; Lunetta, Kathryn L.; Hemminki, Akseli; Dahia, Patricia L M; Sistonen, Pertti; Zheng, Zimu; Caron, Stacey; Van Orsouw, Nathalie J.; Bodmer, Walter F.; Cottrell, Sally E.; Dunlop, Malcolm G.; Eccles, Diana; Hodgson, Shirley V.; Järvinen, Heikki; Kellokumpu, Ilmo; Markie, David; Neale, Kay; Phillips, Robin; Rozen, Paul; Syngal, Sapna; Vijg, Jan; Tomlinson, Ian P M; Aaltonen, Lauri A.; Eng, Charis.

In: Cancer Research, Vol. 57, No. 22, 15.11.1997, p. 5017-5021.

Research output: Contribution to journalArticle

Marsh, DJ, Roth, S, Lunetta, KL, Hemminki, A, Dahia, PLM, Sistonen, P, Zheng, Z, Caron, S, Van Orsouw, NJ, Bodmer, WF, Cottrell, SE, Dunlop, MG, Eccles, D, Hodgson, SV, Järvinen, H, Kellokumpu, I, Markie, D, Neale, K, Phillips, R, Rozen, P, Syngal, S, Vijg, J, Tomlinson, IPM, Aaltonen, LA & Eng, C 1997, 'Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome', Cancer Research, vol. 57, no. 22, pp. 5017-5021.
Marsh DJ, Roth S, Lunetta KL, Hemminki A, Dahia PLM, Sistonen P et al. Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome. Cancer Research. 1997 Nov 15;57(22):5017-5021.
Marsh, Debbie J. ; Roth, Stina ; Lunetta, Kathryn L. ; Hemminki, Akseli ; Dahia, Patricia L M ; Sistonen, Pertti ; Zheng, Zimu ; Caron, Stacey ; Van Orsouw, Nathalie J. ; Bodmer, Walter F. ; Cottrell, Sally E. ; Dunlop, Malcolm G. ; Eccles, Diana ; Hodgson, Shirley V. ; Järvinen, Heikki ; Kellokumpu, Ilmo ; Markie, David ; Neale, Kay ; Phillips, Robin ; Rozen, Paul ; Syngal, Sapna ; Vijg, Jan ; Tomlinson, Ian P M ; Aaltonen, Lauri A. ; Eng, Charis. / Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome. In: Cancer Research. 1997 ; Vol. 57, No. 22. pp. 5017-5021.
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title = "Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome",
abstract = "Juvenile polyposis syndrome (JPS; MIM 174900) is an autosomal dominant condition with incomplete penetrance characterized by hamartomatous polyps of the gastrointestinal tract and a risk of gastrointestinal cancer. Gastrointestinal hamartomatous polyps are also present in Cowden syndrome (CS; MIM 158350) and Bannayan-Zonana syndrome (BZS; also called Ruvalcaba- Myhre-Smith syndrome; MIM 153480). The susceptibility locus for both CS and BZS has recently been identified as the novel tumor suppressor gene PTEN, encoding a dual specificity phosphatase, located at 10q23.3. A putative JPS locus, JP1, which most likely functions as a tumor suppressor, bad previously been mapped to 10q22-24 in both familial and sporadic juvenile polyps. Given the shared clinical features of gastrointestinal hamartomatous polyps among the three syndromes and the coincident mopping of JP1 to the region of PTEN, we sought to determine whether JPS was allelic to CS and BZS by mutation analysis of PTEN and linkage approaches. Microsatellite markers spanning the CS/BZS locus (D10S219, D10S551, D10S579, and D10S541) were used to compute multipoint lod scores in eight informative families with JPS. lod scores of < -2.0 were generated for the entire region, thus excluding PTEN and any genes within the flanking 20-cM interval as candidate loci for familial JPS under our statistical models. In addition, analysis of PTEN using a combination of denaturing gradient gel electrophoresis and direct sequencing was unable to identify a germline mutation in 14 families with JPS and 11 sporadic cases. Therefore, at least a proportion of JPS cases are not caused by germline PTEN alteration or by an alternative locus at 10q22-24.",
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T1 - Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome

AU - Marsh, Debbie J.

AU - Roth, Stina

AU - Lunetta, Kathryn L.

AU - Hemminki, Akseli

AU - Dahia, Patricia L M

AU - Sistonen, Pertti

AU - Zheng, Zimu

AU - Caron, Stacey

AU - Van Orsouw, Nathalie J.

AU - Bodmer, Walter F.

AU - Cottrell, Sally E.

AU - Dunlop, Malcolm G.

AU - Eccles, Diana

AU - Hodgson, Shirley V.

AU - Järvinen, Heikki

AU - Kellokumpu, Ilmo

AU - Markie, David

AU - Neale, Kay

AU - Phillips, Robin

AU - Rozen, Paul

AU - Syngal, Sapna

AU - Vijg, Jan

AU - Tomlinson, Ian P M

AU - Aaltonen, Lauri A.

AU - Eng, Charis

PY - 1997/11/15

Y1 - 1997/11/15

N2 - Juvenile polyposis syndrome (JPS; MIM 174900) is an autosomal dominant condition with incomplete penetrance characterized by hamartomatous polyps of the gastrointestinal tract and a risk of gastrointestinal cancer. Gastrointestinal hamartomatous polyps are also present in Cowden syndrome (CS; MIM 158350) and Bannayan-Zonana syndrome (BZS; also called Ruvalcaba- Myhre-Smith syndrome; MIM 153480). The susceptibility locus for both CS and BZS has recently been identified as the novel tumor suppressor gene PTEN, encoding a dual specificity phosphatase, located at 10q23.3. A putative JPS locus, JP1, which most likely functions as a tumor suppressor, bad previously been mapped to 10q22-24 in both familial and sporadic juvenile polyps. Given the shared clinical features of gastrointestinal hamartomatous polyps among the three syndromes and the coincident mopping of JP1 to the region of PTEN, we sought to determine whether JPS was allelic to CS and BZS by mutation analysis of PTEN and linkage approaches. Microsatellite markers spanning the CS/BZS locus (D10S219, D10S551, D10S579, and D10S541) were used to compute multipoint lod scores in eight informative families with JPS. lod scores of < -2.0 were generated for the entire region, thus excluding PTEN and any genes within the flanking 20-cM interval as candidate loci for familial JPS under our statistical models. In addition, analysis of PTEN using a combination of denaturing gradient gel electrophoresis and direct sequencing was unable to identify a germline mutation in 14 families with JPS and 11 sporadic cases. Therefore, at least a proportion of JPS cases are not caused by germline PTEN alteration or by an alternative locus at 10q22-24.

AB - Juvenile polyposis syndrome (JPS; MIM 174900) is an autosomal dominant condition with incomplete penetrance characterized by hamartomatous polyps of the gastrointestinal tract and a risk of gastrointestinal cancer. Gastrointestinal hamartomatous polyps are also present in Cowden syndrome (CS; MIM 158350) and Bannayan-Zonana syndrome (BZS; also called Ruvalcaba- Myhre-Smith syndrome; MIM 153480). The susceptibility locus for both CS and BZS has recently been identified as the novel tumor suppressor gene PTEN, encoding a dual specificity phosphatase, located at 10q23.3. A putative JPS locus, JP1, which most likely functions as a tumor suppressor, bad previously been mapped to 10q22-24 in both familial and sporadic juvenile polyps. Given the shared clinical features of gastrointestinal hamartomatous polyps among the three syndromes and the coincident mopping of JP1 to the region of PTEN, we sought to determine whether JPS was allelic to CS and BZS by mutation analysis of PTEN and linkage approaches. Microsatellite markers spanning the CS/BZS locus (D10S219, D10S551, D10S579, and D10S541) were used to compute multipoint lod scores in eight informative families with JPS. lod scores of < -2.0 were generated for the entire region, thus excluding PTEN and any genes within the flanking 20-cM interval as candidate loci for familial JPS under our statistical models. In addition, analysis of PTEN using a combination of denaturing gradient gel electrophoresis and direct sequencing was unable to identify a germline mutation in 14 families with JPS and 11 sporadic cases. Therefore, at least a proportion of JPS cases are not caused by germline PTEN alteration or by an alternative locus at 10q22-24.

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