Investigation of the Birt-Hogg-Dube tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer

Nahorski, Michael S.; Lim, Derek; Martin, Lynn; Gille, Johan J. P.; McKay, Kody Zack; Rehal, Pauline K.; Ploeger, H. M.; Steensel, M.A.M. van; Tomlinson, Ian; Latif, Farida; Menko, Fred H.; Maher, Eamonn R.

doi:10.1136/jmg.2009.073304

Cited by 81 publications

(72 citation statements)

References 36 publications

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“…4 The other main additional features of BHD include lung cysts, which can give rise to spontaneous pneumothorax, and polyposis coli, which somehow increases the risk of colon cancer, 5,6 but this is still debated in a recent study. 7 Lipomas and adenomas of the parathyroid glands and oncocytomas of the parotid glands have also been reported with BHD. The gene responsible for this condition is BHD or FLCN, 8 a tumor suppressor gene located on 17p 11.2.…”

Section: Introductionmentioning

confidence: 96%

Syndrome of Birt–Hogg–Dubé, a Histopathological Pitfall With Similarities to Tuberous Sclerosis

Spring

Fellmann²,

Giraud³

et al. 2013

The American Journal of Dermatopathology

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Birt-Hogg-Dubé Syndrome (BHD) is a rare condition, transmitted as an autosomal-dominant trait. The etiology is due to a mutation in the BHD gene, which encodes folliculin (FLCN), located on chromosome 17p. The skin changes observed are benign skin tumors consisting of hamartomas of the hair follicle with dermal changes. Patients with BHD have an increased risk of spontaneous pneumothorax due to rupture of lung cysts and an increased risk of kidney tumors. We report 3 new cases of BHD and discuss their clinical features, histopathological findings, and molecular diagnostics. We highlight the importance of genetic analysis to confirm the diagnosis because of the clinical pitfalls involved in establishing a diagnosis. Finally, we discuss the histopathological features in BHD and tuberous sclerosis complex and focus on their overlapping criterias. A correct diagnosis is essential as it can be life saving for patients.

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Section: Introductionmentioning

confidence: 96%

Syndrome of Birt–Hogg–Dubé, a Histopathological Pitfall With Similarities to Tuberous Sclerosis

Spring

Fellmann²,

Giraud³

et al. 2013

The American Journal of Dermatopathology

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“…Recent studies have also indicated that FLCN suppresses transcription factor E3 and transforming growth factor (TGF)-b, which may additionally lead to the development of renal tumors in BHDS patients [13,14], suggesting a potentially important role for the pathway in tumorigenesis in BHDS. Nahorski et al [15] reported a significantly higher risk of colorectal neoplasia in the analysis of FLCN mutations identified in 149 BHDS patients, and three patients who were carriers of the c.1285dupC mutation developed colorectal malignant neoplasms. This suggests that FLCN inactivation may contribute to colorectal tumorigenesis.…”

Section: Discussionmentioning

confidence: 97%

Possible familial case of Birt–Hogg–Dubé syndrome complicated with lung cancer: A possible link between these two disease entities

Nishida

Yatera

Yamasaki

et al. 2015

Respiratory Medicine

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A 65-year-old Japanese woman was introduced to our hospital for an examination of multiple pulmonary cystic lesions and a pulmonary nodule in the left lower lobe. She had a smoking history of 25 pack-years, and her two younger brothers had suffered from pneumothorax; one of them additionally had lung cancer with pulmonary multiple cystic lesions. A surgical biopsy specimen obtained from her left lower lobe revealed adenocarcinoma surrounded by a single epithelial layer that was covered with collagen fibers. The pathological features were compatible with the findings of the cystic lesions in the patients with Birt-Hogg-Dubé syndrome (BHDS). A diagnosis of BHDS was eventually made according to the detection of a folliculin gene mutation. This is the first report of a possible familial case of BHDS complicated with primary lung cancer. We herein reviewed the previously reported cases of BHDS with lung cancer and other tumors and discussed a potential mechanism of tumorigenesis and carcinogenesis in the lung in the patients with BHDS.

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“…The index case and her brother developed colon cancer before the age of 30 years, possibly when they were even younger than her mother's generation had been at the cancer onset. Nahorski et al suggested that somatic mutations of the FLCN gene in patients with colorectal cancer are "passengers" rather than "driver mutations" (10). If so, the existence of a germline FLCN mutation could have accelerated the malignant transformation of colorectal epithelial cells driven by the "driver," a germline APC mutation of both the index case and her brother.…”

Section: Discussionmentioning

confidence: 99%

Birt-Hogg-Dubé Syndrome and Familial Adenomatous Polyposis: An Association or a Coincidence?

et al. 2012

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An association between Birt-Hogg-Dubé syndrome (BHDS) and colon cancer remains conjectural, but herein we describe a case who may illustrate a significant link between them. The 60-year-old woman was diagnosed at 28 years of age with colon carcinoma and familial adenomatous polyposis (FAP). She also had repeated pneumothoraces, and was diagnosed with BHDS following the finding of pneumothorax in her son. We confirmed the presence of germline mutations in both her folliculin (FLCN) and adenomatous polyposis coli (APC) genes. The family pedigree suggested that a de novo FLCN mutation might have contributed to the development of colon carcinoma at a younger age than her family members.

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Investigation of the Birt-Hogg-Dube tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer

Cited by 81 publications

References 36 publications

Syndrome of Birt–Hogg–Dubé, a Histopathological Pitfall With Similarities to Tuberous Sclerosis

Syndrome of Birt–Hogg–Dubé, a Histopathological Pitfall With Similarities to Tuberous Sclerosis

Possible familial case of Birt–Hogg–Dubé syndrome complicated with lung cancer: A possible link between these two disease entities

Birt-Hogg-Dubé Syndrome and Familial Adenomatous Polyposis: An Association or a Coincidence?

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