G2Cdb::Human Disease report

Disease id
D00000117
Name
Myelodysplastic syndrome
Nervous system disease
no

Genes (2)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00000036 NF1
neurofibromin 1
Y (1568247) Microinsertion (MI) Y
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (12717436) Single nucleotide polymorphism (SNP) Y
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (12717436) Microinsertion (MI) Y
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (12717436) Trinucleotide substitution (TriNS) Y
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (15009076) Unknown (?) N
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (15282682) No mutation found (N) N
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (15725481) Unknown (?) ?
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (17339262) Deletion (D) Y
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (17339262) Translocation (T) Y

References

  • Patients with functional constipation do not have increased prevalence of colorectal cancer precursors.

    Chan AO, Hui WM, Leung G, Tong T, Hung IF, Chan P, Hsu A, But D, Wong BC, Lam SK and Lam KF

    Gut 2007;56;3;451-2

  • Acquired PTPN11 mutations occur rarely in adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia.

    Loh ML, Martinelli S, Cordeddu V, Reynolds MG, Vattikuti S, Lee CM, Wulfert M, Germing U, Haas P, Niemeyer C, Beran ME, Strom S, Lübbert M, Sorcini M, Estey EH, Gattermann N and Tartaglia M

    Department of Pediatrics, University of California, San Francisco, CA, USA.

    Myelodysplastic syndromes (MDS) are comprised of a heterogeneous group of stem cell disorders characterized by ineffective hematopoiesis and susceptibility to transform to acute myeloid leukemia. The molecular pathways underlying disease initiation and evolution are still largely unknown. We recently demonstrated that acquired mutations in PTPN11 are a major event in JMML and occur with variable prevalence in children with other hematologic malignancies, including MDS. Here, we investigated contribution of PTPN11 mutations to adult MDS and CMML pathogenesis. Our results indicate that PTPN11 lesions might play a role in adult MDS/CMML pathogenesis but do not represent a major molecular event.

    Funded by: Telethon: GGP04172

    Leukemia research 2005;29;4;459-62

  • Mutations in PTPN11 are rare in adult myelodysplastic syndromes and acute myeloid leukemia.

    Watkins F, Fidler C, Boultwood J and Wainscoat JS

    American journal of hematology 2004;76;4;417

  • Mutations in PTPN11 are uncommon in adult myelodysplastic syndromes and acute myeloid leukaemia.

    Johan MF, Bowen DT, Frew ME, Goodeve AC, Wilson GA, Peake IR and Reilly JT

    British journal of haematology 2004;124;6;843-4

  • Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia.

    Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, Hählen K, Hasle H, Licht JD and Gelb BD

    Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA.

    We report here that individuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML) have germline mutations in PTPN11 and that somatic mutations in PTPN11 account for 34% of non-syndromic JMML. Furthermore, we found mutations in PTPN11 in a small percentage of individuals with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML). Functional analyses documented that the two most common mutations in PTPN11 associated with JMML caused a gain of function.

    Nature genetics 2003;34;2;148-50

  • Somatic mutations in the neurofibromatosis 1 gene in human tumors.

    Li Y, Bollag G, Clark R, Stevens J, Conroy L, Fults D, Ward K, Friedman E, Samowitz W, Robertson M et al.

    Department of Human Genetics, University of Utah School of Medicine, Salt Lake City 84112.

    The neurofibromatosis 1 (NF1) gene product, neurofibromin, contains a GTPase-activating protein (GAP)-related domain, or NF1 GRD, that is able to down-regulate p21ras by stimulating its intrinsic GTPase. Since p21ras.GTP is a major regulator of growth and differentiation, mutant neurofibromins resulting from somatic mutations in the NF1 gene might interfere with ras signaling pathways and contribute to the development of tumors. We describe an amino acid substitution in the NF1 GRD, altering Lys-1423, that has occurred in three tumor types: colon adenocarcinoma, myelodysplastic syndrome, and anaplastic astrocytoma, and in one family with neurofibromatosis 1. The GAP activity of the mutant NF1 GRD is 200- to 400-fold lower than that of wild type, whereas binding affinity is unaffected. Thus, germline mutations in NF1 that cause neurofibromatosis 1 can also occur in somatic cells and contribute to the development of sporadic tumors, including tumors not associated with neurofibromatosis 1.

    Cell 1992;69;2;275-81

Literature (6)

Pubmed - human_disease

  • Patients with functional constipation do not have increased prevalence of colorectal cancer precursors.

    Chan AO, Hui WM, Leung G, Tong T, Hung IF, Chan P, Hsu A, But D, Wong BC, Lam SK and Lam KF

    Gut 2007;56;3;451-2

  • Mutations in PTPN11 are uncommon in adult myelodysplastic syndromes and acute myeloid leukaemia.

    Johan MF, Bowen DT, Frew ME, Goodeve AC, Wilson GA, Peake IR and Reilly JT

    British journal of haematology 2004;124;6;843-4

Pubmed - other

  • Acquired PTPN11 mutations occur rarely in adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia.

    Loh ML, Martinelli S, Cordeddu V, Reynolds MG, Vattikuti S, Lee CM, Wulfert M, Germing U, Haas P, Niemeyer C, Beran ME, Strom S, Lübbert M, Sorcini M, Estey EH, Gattermann N and Tartaglia M

    Department of Pediatrics, University of California, San Francisco, CA, USA.

    Myelodysplastic syndromes (MDS) are comprised of a heterogeneous group of stem cell disorders characterized by ineffective hematopoiesis and susceptibility to transform to acute myeloid leukemia. The molecular pathways underlying disease initiation and evolution are still largely unknown. We recently demonstrated that acquired mutations in PTPN11 are a major event in JMML and occur with variable prevalence in children with other hematologic malignancies, including MDS. Here, we investigated contribution of PTPN11 mutations to adult MDS and CMML pathogenesis. Our results indicate that PTPN11 lesions might play a role in adult MDS/CMML pathogenesis but do not represent a major molecular event.

    Funded by: Telethon: GGP04172

    Leukemia research 2005;29;4;459-62

  • Mutations in PTPN11 are rare in adult myelodysplastic syndromes and acute myeloid leukemia.

    Watkins F, Fidler C, Boultwood J and Wainscoat JS

    American journal of hematology 2004;76;4;417

  • Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia.

    Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, Hählen K, Hasle H, Licht JD and Gelb BD

    Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA.

    We report here that individuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML) have germline mutations in PTPN11 and that somatic mutations in PTPN11 account for 34% of non-syndromic JMML. Furthermore, we found mutations in PTPN11 in a small percentage of individuals with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML). Functional analyses documented that the two most common mutations in PTPN11 associated with JMML caused a gain of function.

    Nature genetics 2003;34;2;148-50

  • Somatic mutations in the neurofibromatosis 1 gene in human tumors.

    Li Y, Bollag G, Clark R, Stevens J, Conroy L, Fults D, Ward K, Friedman E, Samowitz W, Robertson M et al.

    Department of Human Genetics, University of Utah School of Medicine, Salt Lake City 84112.

    The neurofibromatosis 1 (NF1) gene product, neurofibromin, contains a GTPase-activating protein (GAP)-related domain, or NF1 GRD, that is able to down-regulate p21ras by stimulating its intrinsic GTPase. Since p21ras.GTP is a major regulator of growth and differentiation, mutant neurofibromins resulting from somatic mutations in the NF1 gene might interfere with ras signaling pathways and contribute to the development of tumors. We describe an amino acid substitution in the NF1 GRD, altering Lys-1423, that has occurred in three tumor types: colon adenocarcinoma, myelodysplastic syndrome, and anaplastic astrocytoma, and in one family with neurofibromatosis 1. The GAP activity of the mutant NF1 GRD is 200- to 400-fold lower than that of wild type, whereas binding affinity is unaffected. Thus, germline mutations in NF1 that cause neurofibromatosis 1 can also occur in somatic cells and contribute to the development of sporadic tumors, including tumors not associated with neurofibromatosis 1.

    Cell 1992;69;2;275-81

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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