Feminizing Sertoli Cell Tumors in Boys with Peutz-Jeghers Syndrome

Young, Stephanie; Gooneratne, S; Straus, Francis H.; Zeller, W. P.; Bulun, Serdar E.; Rosenthal, Ira

doi:10.1097/00000478-199501000-00007

Cited by 132 publications

(73 citation statements)

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“…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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“…83 In terms of the testis, the sex cords are the site of tumorigenesis and a total of 35 boys with PJS have presented with testicular Sertoli cell tumors. 36,37,39,59,81,[84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100] In boys with PJS, there is an increase of aromatase expression and activity in these tumors, resulting in excess estradiol production that not only acts to feed local tumor growth, 36,39 but also accelerates testicular and extragonadal morphogenesis. For instance, the obvious clinical manifestations are enlarged testes, pre-pubertal gynecomastia and feminizing precocious puberty, and it has become increasingly numbers and the fact that spermatozoa in these mice display decreased motility, as evidenced by the proven inability to fertilize oocytes in vitro.…”

Section: Clinical Casesmentioning

confidence: 99%

“…67 Microscopically, SCTATs result in clusters of enlarged annular seminiferous tubules nestled among seminiferous tubules of normal size and appearance. 100 The enlarged seminiferous tubules are composed of hypertrophied Sertoli cells enclosed by a thickened basement membrane, with no evidence of germ cells. 100 Moreover, the tumors in boys with PJS can in some instances show signs of calcification distributed throughout the tumor, which is a hallmark for the diagnosis of a large cell calcifying Sertoli cell tumor (LCCSCT).…”

Section: Arommentioning

confidence: 99%

“…100 The enlarged seminiferous tubules are composed of hypertrophied Sertoli cells enclosed by a thickened basement membrane, with no evidence of germ cells. 100 Moreover, the tumors in boys with PJS can in some instances show signs of calcification distributed throughout the tumor, which is a hallmark for the diagnosis of a large cell calcifying Sertoli cell tumor (LCCSCT). 100 Together, SCTAT and LCCSCT classically comprise the two tumor types observed in boys with PJS.…”

Section: Arommentioning

confidence: 99%

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Teasing out the role of aromatase in the healthy and diseased testis

Haverfield

Ham

Brown³

et al. 2011

Spermatogenesis

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“…Testicular sex cord and Sertoli-cell tumours may occur in prepubertal boys affected with PJS leading to sexual precocity and gynaecomastia (Wilson et al, 1986;Coen et al, 1991;Young et al, 1995). The production of oestrogen in ovarian tumours in girls with PJS has also been reported causing isosexual precocity (Sohl et al, 1983).…”

mentioning

confidence: 99%

Further observations on LKB1/STK11 status and cancer risk in Peutz–Jeghers syndrome

et al. 2003

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Germline mutations in the LKB1/STK11 tumour suppressor gene cause Peutz -Jeghers syndrome (PJS), a rare dominant disorder. In addition to typical hamartomatous gastrointestinal polyps and pigmented perioral lesions, PJS is associated with an increased risk of tumours at multiple sites. Follow-up information on carriers is limited and genetic heterogeneity makes counselling and management in PJS difficult. Here we report the analysis of the LKB1/STK11 locus in a series of 33 PJS families, and estimation of cancer risks in carriers and noncarriers. Germline mutations of LKB1/STK11 were identified in 52% of cases. This observation reinforces the hypothesis of a second PJS locus. In carriers of LKB1/STK11 mutations, the risk of cancer was markedly elevated. The risk of developing any cancer in carriers by age 65 years was 47% (95% CI: 27 -73%) with elevated risks of both gastrointestinal and breast cancer. PJS with germline mutations in LKB1/STK11 are at a very high relative and absolute risk of multiple gastrointestinal and nongastrointestinal cancers. To obtain precise estimates of risk associated with PJS requires further studies of genotype -phenotype especially with respect to LKB1/STK11 negative cases, as this group is likely to be heterogeneous.

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Feminizing Sertoli Cell Tumors in Boys with Peutz-Jeghers Syndrome

Cited by 132 publications

References 0 publications

LKB1; linking cell structure and tumor suppression

LKB1; linking cell structure and tumor suppression

Teasing out the role of aromatase in the healthy and diseased testis

Further observations on LKB1/STK11 status and cancer risk in Peutz–Jeghers syndrome

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