Annual review 2016

2016 has been a busy year for BHD research. With the new year approaching, this week’s blog will review the studies we’ve particularly enjoyed writing about and revisit the year’s highlights.

Iribe et al. (2016) assessed several RCC subtypes from BHD patients to determine if they had similar or distinct patterns of genetic abnormalities. Only a few chromophobe RCC and clear cell RCC samples showed variation in chromosomal copy number. However, all subtypes had various areas of loss of heterogeneity.  Kato et al. (2016) assessed whether variability in chromosomal status could be used to identify BHD-associated RCC: they found that the status of chromosome 17 was useful in distinguishing BHD-associated hybrid oncocytic/chromophobe tumours (HOCT) and chromophobe RCC from sporadic chromophobe RCC.  Furuya et al. (2016) established a new cell line from a BHD patient’s chromophobe RCC.

A very comprehensive review from Kennedy et al. (2016) summarised the current understanding of BHD pulmonary pathology relative to the stretch hypothesis for cyst formation. Gupta et al. (2016b) published a review exploring the key points and research advances in BHD genetics and pathogenesis, clinical manifestations, diagnosis and disease management.

Starling et al. (2016) showed that FLCN controls the dynamic cytoplasmic position of lysosomes. Starvation‐induced FLCN association with lysosomes drives the formation of contact sites between lysosomes and Rab34‐positive peri-nuclear membranes.  Zhong et al. (2016) described FLCN as a ciliary protein that regulates mTORC1 through primary cilia: they showed that FLCN recruits LKB1 to primary cilia for activation of AMPK, causing mTORC1 down-regulation. Yan et al. (2016) and Wada et al. (2016)  showed that FLCN regulates the browning of adipose tissue via a non-canonical mTOR pathway.  Woodford et al. (2016) showed that the stability of FLCN is dependent on the chaperone function of Hsp90. The authors reported that FNIPs act as co-chaperones of Hsp90 by regulating its ATPase activity and chaperoning. Kenyon et al. (2016) examined the role of FLCN in zebrafish development using morpholino oligonucleotides to generate a zebrafish BHD model.

Hoshika et al. (2016) isolated lung fibroblasts from BHD patients. They showed that FLCN is associated with chemotaxis in lung fibroblasts and that, together with reduced TGF-β1 expression by BHD lung fibroblasts, FLCN haploinsufficiency seems to cause lung fibroblast dysfunction, impairing tissue repair.

Dong et al. (2016)  reported two BHD patients also affected with papillary thyroid cancer. The authors recommended neck ultrasound for BHD patients and families and suggest an investigation to evaluate the prevalence of thyroid cancer in patients with BHD. There is currently insufficient evidence to associate thyroid cancer and other thyroid conditions with BHD. However, all the studies mentioned in the post suggest a possible link between the two that should be considered for future research.

A study by Whitworth et al. (2016) reported new cases of multiple germline mutations in inherited cancer syndrome genes involving the combination of mutations in FLCN with mutations in other genes. Authors suggest that clinicians should consider this phenomenon in patients with unexpected inherited cancer syndrome phenotypes.

In the autumn, a new study by Johannesma et al. (2016) evaluated the incidence of spontaneous pneumothorax (SP) in patients with BHD during or shortly after air travel and diving. The data suggested that patients might possibly have an increased risk for pneumothorax in flying and diving.  Gupta et al. (2016) evaluated the cost-effectiveness of high resolution computed tomographic (HRCT) chest imaging for early diagnosis of LAM, BHD, and PLCH in patients presenting with an apparent primary SP. The authors showed that HRCT image screening is cost-effective and suggest that clinicians should consider performing it in these patients to lead to appropriate management approaches.

During the year, several new case studies were reported worldwide. You can find them in our BHD Article Library: Clinical Research.

In addition, we wrote about the updates on clinical trials for BHD and RCC.

We have also attended conferences and workshops including The International RLDC and LAM symposium, the Cilia 2016 and Findacure workshops. These events represent wonderful opportunities to meet researchers, patients and advocates, and to hear about projects helping rare disease research.

Finally, we have redesigned our website. The objectives of the new design were aesthetics, facilitating the navigation and having a responsive layout for all platforms. It also includes an updated and more interactive FLCN signalling pathway.

We at the BHD Foundation are very much looking forward to seeing how the BHD research field develops in 2017. We wish all our readers a very Happy New Year.

  • Gupta, N., Sunwoo, B., & Kotloff, R. (2016). Birt-Hogg-Dubé Syndrome Clinics in Chest Medicine, 37 (3), 475-486 DOI: 10.1016/j.ccm.2016.04.010
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