Relative frequency and morphology of cancers in STK11 mutation carriers1 ☆

Lim, Wendy; Olschwang, Sylviane; Keller, Josbert J.; Westerman, Anne Marie; Menko, Fred H.; Boardman, Lisa A.; Scott, Rodney J.; Trimbath, Jill D.; Giardiello, Francis M.; Gruber, Stephen B.; Gille, Johan J. P.; Offerhaus, G.J.A.; Rooij, Felix W.M. de; Wilson, J. H. P.; Spigelman, Allan D.; Phillips, R. K. S.; Houlston, Richard S.

doi:10.1053/j.gastro.2004.03.014

Cited by 221 publications

(134 citation statements)

References 38 publications

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“…Although there is a possibility that these could transform to become carcinomas, there are several lines of evidence suggesting otherwise and that this aspect of PJS might be functionally separate from the role of LKB1 in suppressing malignant transformation (see below; 'Benign and malignant tumorigenesis'). A markedly increased incidence of carcinomas of the gastrointestinal tract including stomach, small bowel, colon and pancreatic cancer, as well as breast, ovary, uterus, cervix, lung and testis cancer has been observed through longitudinal studies of affected kindreds (Giardiello et al, 1987(Giardiello et al, , 2000Spigelman et al, 1989;Gruber et al, 1998;Lim et al, 2004;Hearle et al, 2006). In addition, rare tumors have been associated with PJS including those of a reproductive origin-including testicular and ovarian sex cord tumors, Sertoli cell tumors and adenoma malignum of the cervix-as well as non-adenocarcinoma pancreatic tumors, including pancreatic intraductal papillary mucinous neoplasia and serous cystadenomas (Podczaski et al, 1991;Young et al, 1995;Tomlinson and Houlston, 1997;Su et al, 1999;Sato et al, 2001;Yee et al, 2003).…”

Section: Peutz-jeghers Syndrome and Human Cancer Geneticsmentioning

confidence: 99%

LKB1; linking cell structure and tumor suppression

2008

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Germ line mutations in the LKB1 tumor suppressor gene are associated with the Peutz-Jeghers polyposis and cancer syndrome. Somatic mutations in Lkb1 are observed in sporadic pulmonary, pancreatic and biliary cancers and melanomas. The LKB1 serine-threonine kinase functionally and biochemically links control of cellular structure and energy utilization through activation of the AMPK family of kinases. Lkb1 regulates cell polarity through downstream kinases including AMPKs, MARKs and BRSKs, and nutrient utilization and cellular metabolism through the AMPK-mTOR pathway. LKB1 has been shown to affect normal chromosomal segregation, TGF-b signaling in the mesenchyme and WNT and p53 activity. Although each of the LKB1-dependent processes and downstream pathways have been individually delineated through work across a range of experimental systems, how they relate to Lkb1's role as a tumor suppressor remains to be fully explored and elucidated. The recent development of mouse cancer models harboring engineered mutations in Lkb1 have offered insights into how LKB1 may be functioning to restrain tumorigenesis and how its role as a master regulator of polarity and metabolism could contribute to its tumor suppressor function.

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Section: Peutz-jeghers Syndrome and Human Cancer Geneticsmentioning

confidence: 99%

LKB1; linking cell structure and tumor suppression

2008

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“…These differences are puzzling because lung cancer risk is higher but is not among the commonest tumors that occur in PJS. Before ruling out the LKB1 tumor-suppressor role in sporadic tumors other than in lung, the obstacles associated with the detection of mutations in tumors need to be b Stomach a LKB1 PROTEIN EXPRESSION (Luuko et al 1999;Rowan et al 2000Conde et al 2007 (Giardiello et alet al 2000;Lim et al 2004;Hearle et al 2006a) …”

Section: Lkb1 and Peutz-jeghers Syndromementioning

confidence: 99%

A role for LKB1 gene in human cancer beyond the Peutz–Jeghers syndrome

2007

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“…7 In addition, it is widely recognised that genetic susceptibility can be a major cause of MPMT and many monogenic familial cancer syndromes are associated with a high frequency of this phenomenon. [8][9][10][11][12] Indeed, particular combinations of multiple tumours may suggest specific cancer syndromes (eg haemangioblastomas and renal cancers in von Hippel-Lindau disease). Accordingly, many patients with MPMT will be referred for clinical genetics evaluation because of a suspicion of such a syndrome.…”

Section: Introductionmentioning

confidence: 99%

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

et al. 2014

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Multiple primary malignant tumours (MPMT) are frequently taken as an indicator of potential inherited cancer susceptibility and occur at appreciable frequency both among unselected cancer patients and, particularly, among referrals to cancer genetics services. However, there is a paucity of information on the clinical genetic evaluation of cohorts of MPMT patients representing a variety of tumour types. We ascertained a referral-based series of MPMT cases and describe the patterns of tumours observed. Service-based molecular genetic testing had demonstrated a pathogenic germline variant in an inherited cancer gene in fewer than one in four unselected referrals. To assess for evidence of thus far unidentified variants in those who tested negative, comparisons were made with those who tested positive. This revealed considerable overlap between the two groups with respect to clinical characteristics indicative of an inherited cancer syndrome. We therefore proceeded to test a subset of unexplained MPMT cases (n ¼ 62) for pathogenic germline variants in TP53 and PTEN but none were detected. Individuals with MPMT may receive negative genetic test results for a number of reasons, which are discussed. Many of these may be addressed by the increasing application of next generation sequencing techniques such as inherited cancer gene panels.

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Relative frequency and morphology of cancers in STK11 mutation carriers1 ☆

Cited by 221 publications

References 38 publications

LKB1; linking cell structure and tumor suppression

LKB1; linking cell structure and tumor suppression

A role for LKB1 gene in human cancer beyond the Peutz–Jeghers syndrome

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

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