Somatic mutations in the Peutz-Jeghers (LKB1/STK11) gene in sporadic malignant melanomas


Rowan, Andrew, Bataille, Veronique, MacKie, Rona, Healy, Eugene, Bicknell , David, Bodmer, Walter and Tomlinson, Ian (1999) Somatic mutations in the Peutz-Jeghers (LKB1/STK11) gene in sporadic malignant melanomas. Journal of Investigative Dermatology, 112, (4), 509-511. (doi:10.1046/j.1523-1747.1999.00551.x). (PMID:10201537).

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Description/Abstract

Germline mutations in the LKB1/STK11 gene cause characteristic hamartomas and freckling to develop in patients with Peutz-Jeghers syndrome (PJS). The hamartomas arise as a result of somatic "second hits" at LKB1/STK11 and therefore contain a neoplastic element. The origin of the pigmented lesions in PJS is unknown and difficult to test, as these are hardly ever biopsied. PJS patients are at increased risk of benign and malignant tumors, particularly of the colon, breast, pancreas, testis, and ovary, although the increased risk for any one of these sites may be quite modest. Somatic LKB1/STK11 mutations have been found, albeit at a low frequency, in sporadic tumors of the colon, stomach, ovary, and testis. Although PJS patients are not known to have an excess of skin tumors, if the freckles of PJS patients are actually small, benign tumors, LKB1/STK11 mutations must provide these lesions with a selective advantage, and similar mutations might also give a selective advantage to related malignant tumors, such as melanomas. We have therefore screened 16 melanoma cell lines, 15 primary melanomas, and 19 metastases for LKB1/STK11 mutations. Two LKB1/STK11 mutations were found: a missense change (Y49D) accompanied by allele loss in a cell line; and a missense change(G135R), without a detected mutation in the other allele, in a primary tumor. Both these mutations are highly likely to be pathogenic. Novel polymorphisms, including an unusual heptanucleotide repeat, were also found in introns 2 and 3. LKB1/STK11 mutations occur in a significant minority of tumors of several sites, including malignant melanomas.

Item Type: Article
ISSNs: 0022-202X (print)
1523-1747 (electronic)
Subjects: R Medicine > RB Pathology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RL Dermatology
Divisions: Faculty of Medicine > Infection, Inflammation and Immunity
ePrint ID: 334272
Date Deposited: 16 Mar 2012 10:18
Last Modified: 27 Mar 2014 20:19
URI: http://eprints.soton.ac.uk/id/eprint/334272

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