A serine/threonine kinase gene defective in Peutz-Jeghers syndrome

A Hemminki; D Markie; I Tomlinson; E McDonald; S Roth; A Loukola; G Bignell; W Warren; M Aminoff; P Höglund; H Järvinen; P Kristo; K Pelin; M Ridanpää; R Salovaara; T Toro; W Bodmer; S Olschwang; A S Olsen; M R Stratton; A de la Chapelle; L A Aaltonen

doi:10.1038/34432

A serine/threonine kinase gene defective in Peutz-Jeghers syndrome

A Hemminki, D Markie, I Tomlinson, E McDonald, S Roth, A Loukola, G Bignell, W Warren, M Aminoff, P Höglund, H Järvinen, P Kristo, K Pelin, M Ridanpää, R Salovaara, T Toro, W Bodmer, S Olschwang, A S Olsen, M R StrattonA de la Chapelle, L A Aaltonen

Division of Cancer Sciences (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

Studies of hereditary cancer syndromes have contributed greatly to our understanding of molecular events involved in tumorigenesis. Here we investigate the molecular background of the Peutz-Jeghers syndrome (PJS), a rare hereditary disease in which there is predisposition to benign and malignant tumours of many organ systems. A locus for this condition was recently assigned to chromosome 19p. We have identified truncating germline mutations in a gene residing on chromosome 19p in multiple individuals affected by PJS. This previously identified but unmapped gene, LKB1, has strong homology to a cytoplasmic Xenopus serine/threonine protein kinase XEEK1, and weaker similarity to many other protein kinases. Peutz-Jeghers syndrome is therefore the first cancer-susceptibility syndrome to be identified that is due to inactivating mutations in a protein kinase.

Original language	English
Pages (from-to)	184-7
Number of pages	4
Journal	Nature
Volume	391
Issue number	6663
DOIs	https://doi.org/10.1038/34432
Publication status	Published - 8 Jan 1998

Keywords

Amino Acid Sequence
Cell Line
Chromosome Mapping
Chromosomes, Human, Pair 19
Female
Germ-Line Mutation
Humans
Male
Molecular Sequence Data
Pedigree
Peutz-Jeghers Syndrome
Polymerase Chain Reaction
Protein-Serine-Threonine Kinases
Sequence Homology, Amino Acid
Xenopus Proteins
Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/34432

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Hemminki, A., Markie, D., Tomlinson, I., McDonald, E., Roth, S., Loukola, A., Bignell, G., Warren, W., Aminoff, M., Höglund, P., Järvinen, H., Kristo, P., Pelin, K., Ridanpää, M., Salovaara, R., Toro, T., Bodmer, W., Olschwang, S., Olsen, A. S., ... Aaltonen, L. A. (1998). A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature, 391(6663), 184-7. https://doi.org/10.1038/34432

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title = "A serine/threonine kinase gene defective in Peutz-Jeghers syndrome",

abstract = "Studies of hereditary cancer syndromes have contributed greatly to our understanding of molecular events involved in tumorigenesis. Here we investigate the molecular background of the Peutz-Jeghers syndrome (PJS), a rare hereditary disease in which there is predisposition to benign and malignant tumours of many organ systems. A locus for this condition was recently assigned to chromosome 19p. We have identified truncating germline mutations in a gene residing on chromosome 19p in multiple individuals affected by PJS. This previously identified but unmapped gene, LKB1, has strong homology to a cytoplasmic Xenopus serine/threonine protein kinase XEEK1, and weaker similarity to many other protein kinases. Peutz-Jeghers syndrome is therefore the first cancer-susceptibility syndrome to be identified that is due to inactivating mutations in a protein kinase.",

keywords = "Amino Acid Sequence, Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 19, Female, Germ-Line Mutation, Humans, Male, Molecular Sequence Data, Pedigree, Peutz-Jeghers Syndrome, Polymerase Chain Reaction, Protein-Serine-Threonine Kinases, Sequence Homology, Amino Acid, Xenopus Proteins, Journal Article, Research Support, Non-U.S. Gov't",

author = "A Hemminki and D Markie and I Tomlinson and E McDonald and S Roth and A Loukola and G Bignell and W Warren and M Aminoff and P H{\"o}glund and H J{\"a}rvinen and P Kristo and K Pelin and M Ridanp{\"a}{\"a} and R Salovaara and T Toro and W Bodmer and S Olschwang and Olsen, {A S} and Stratton, {M R} and {de la Chapelle}, A and Aaltonen, {L A}",

year = "1998",

month = jan,

day = "8",

doi = "10.1038/34432",

language = "English",

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pages = "184--7",

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Hemminki, A, Markie, D, Tomlinson, I, McDonald, E, Roth, S, Loukola, A, Bignell, G, Warren, W, Aminoff, M, Höglund, P, Järvinen, H, Kristo, P, Pelin, K, Ridanpää, M, Salovaara, R, Toro, T, Bodmer, W, Olschwang, S, Olsen, AS, Stratton, MR, de la Chapelle, A & Aaltonen, LA 1998, 'A serine/threonine kinase gene defective in Peutz-Jeghers syndrome', Nature, vol. 391, no. 6663, pp. 184-7. https://doi.org/10.1038/34432

TY - JOUR

T1 - A serine/threonine kinase gene defective in Peutz-Jeghers syndrome

AU - Hemminki, A

AU - Markie, D

AU - Tomlinson, I

AU - McDonald, E

AU - Roth, S

AU - Loukola, A

AU - Bignell, G

AU - Warren, W

AU - Aminoff, M

AU - Höglund, P

AU - Järvinen, H

AU - Kristo, P

AU - Pelin, K

AU - Ridanpää, M

AU - Salovaara, R

AU - Toro, T

AU - Bodmer, W

AU - Olschwang, S

AU - Olsen, A S

AU - Stratton, M R

AU - de la Chapelle, A

AU - Aaltonen, L A

PY - 1998/1/8

Y1 - 1998/1/8

N2 - Studies of hereditary cancer syndromes have contributed greatly to our understanding of molecular events involved in tumorigenesis. Here we investigate the molecular background of the Peutz-Jeghers syndrome (PJS), a rare hereditary disease in which there is predisposition to benign and malignant tumours of many organ systems. A locus for this condition was recently assigned to chromosome 19p. We have identified truncating germline mutations in a gene residing on chromosome 19p in multiple individuals affected by PJS. This previously identified but unmapped gene, LKB1, has strong homology to a cytoplasmic Xenopus serine/threonine protein kinase XEEK1, and weaker similarity to many other protein kinases. Peutz-Jeghers syndrome is therefore the first cancer-susceptibility syndrome to be identified that is due to inactivating mutations in a protein kinase.

AB - Studies of hereditary cancer syndromes have contributed greatly to our understanding of molecular events involved in tumorigenesis. Here we investigate the molecular background of the Peutz-Jeghers syndrome (PJS), a rare hereditary disease in which there is predisposition to benign and malignant tumours of many organ systems. A locus for this condition was recently assigned to chromosome 19p. We have identified truncating germline mutations in a gene residing on chromosome 19p in multiple individuals affected by PJS. This previously identified but unmapped gene, LKB1, has strong homology to a cytoplasmic Xenopus serine/threonine protein kinase XEEK1, and weaker similarity to many other protein kinases. Peutz-Jeghers syndrome is therefore the first cancer-susceptibility syndrome to be identified that is due to inactivating mutations in a protein kinase.

KW - Amino Acid Sequence

KW - Cell Line

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 19

KW - Female

KW - Germ-Line Mutation

KW - Humans

KW - Male

KW - Molecular Sequence Data

KW - Pedigree

KW - Peutz-Jeghers Syndrome

KW - Polymerase Chain Reaction

KW - Protein-Serine-Threonine Kinases

KW - Sequence Homology, Amino Acid

KW - Xenopus Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/34432

DO - 10.1038/34432

M3 - Article

C2 - 9428765

SN - 1476-4687

VL - 391

SP - 184

EP - 187

JO - Nature

JF - Nature

IS - 6663

ER -

A serine/threonine kinase gene defective in Peutz-Jeghers syndrome

Abstract

Keywords

UN SDGs

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