Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition

Multifactorial predisposition to melanoma includes genes involved in pigmentation, immunity and DNA repair. Nonetheless, missing heritability in melanoma is still important. We studied the role of 335 candidate SNPs in melanoma susceptibility by using a dedicated chip and investigating 110 genes involved in different pathways. A discovery set was comprised of 1069 melanoma patients and 925 controls from France. Data were replicated using validation phases II (1085 cases and 801 controls from Spain) and III (1808 cases and 1894 controls from Germany and a second set of Spanish samples). In addition, an exome sequencing study was performed in three high‐risk French melanoma families. Nineteen SNPs in 17 genes were initially associated with melanoma in the French population. Six SNPs were replicated in phase II, including two new SNPs in the WNT3 (rs199524) and VPS41 (rs11773094) genes. The role of VPS41 and WNT3 was confirmed in a meta‐analysis (3940 melanoma cases and 3620 controls) with two‐side p values of 0.002, (OR = 0.86) and 4.07 × 10^?10 (OR = 0.80), respectively. Exome sequencing revealed a non‐synonymous VPS41 variant in one family that was shown to be strongly associated with familial melanoma (OR = 4.46, p = 0.001) in an independent sample of 178 melanoma families. WNT3 belongs to WNT pathway known to play a crucial role in melanoma, whereas VPS41 regulates vesicular trafficking and is thought to play a role in pigmentation. Our work identified two new pathways involved in melanoma predisposition. These results may be useful in the future for identifying individuals highly predisposed to melanoma.     

Peritoneal amyloidosis: unusual localization of gastrointestinal amyloidosis

Amyloidosis is a rare disease that results from the extracellular deposition of amorphous fibrillar protein. It is usually observed in a systemic form. Gastrointestinal involvement is frequent but peritoneal localization is unusual. A 43-year-old male was investigated for nephritic colic. Morphologic explorations revealed small intestine agglomerans in the periumbilical region, infiltration of peritoneal fat and multiple coelio-mesenteric lymph nodes. There were no clinical or biological abnormalities and endoscopic examinations were normal. The patient then underwent an exploratory laparoscopy. Macroscopically false membranes were seen throughout the peritoneum and small bowel without ascites. Anatomopathologic examination diagnosed peritoneal amyloidosis. After several investigations a diagnosis of a primary peritoneal amyloidosis was confirmed. The patient was treated with melphalan and prednisone with a favorable outcome. Our case illustrates a particular presentation of peritoneal amyloidosis. Despite improved imaging methods, peritoneal biopsy remains essential for diagnosis.     

Evidence of human papillomavirus in the placenta

Human papillomavirus (HPV) is an epitheliotropic virus typically infecting keratinocytes but also possibly epithelial trophoblastic placental cells. In the present study, we set out to investigate whether HPV can be recovered from transabdominally obtained placental cells to avoid any confounding contamination by HPV-infected cervical cells. Thirty-five placental samples from women undergoing transabdominal chorionic villous sampling were analyzed, and we detected HPV-16 and HPV-62 in 2 placentas. This study suggests that HPV infection of the placenta can occur early in pregnancy. The overall clinical implication of these results remains to be elucidated.     

Giant hydatid lung cysts: About two paediatric cases

Cystic echinococcosis, which commonly starts during childhood or adolescence, is a serious problem of public health in Tunisia. The resulting large cysts in the lung are a special clinical entity called giant hydatid cysts. Herein we present two paediatric cases of this rare entity. In the first case a fourteen-year-old boy presented with chest pain, thoracic deformation, weight loss and dyspnea revealing two giant hydatid cysts of the upper and the lower lobes of the right lung. In the second case, a seven-year-old girl presented with chest pain, dyspnea, fever and episodes of suffocation revealing a giant hydatid cyst of the right upper lobe of the lung.The three giant cysts were non-complicated, they were treated by cystotomy and capitonnage without post-operative complications and without recurrence of the disease on follow-up.     

Letter: Intestinal heterotopia in urethral caruncle

We report a case of urethral caruncle with intestinal heterotopia in a 26-year-old woman. This entity is rarely reported.     

Relationship between toll-like receptor 2 nonsynonymous single nucleotide polymorphisms and the effectiveness of Bacille Calmette-Guérin immunotherapy in preventing recurrence of superficial bladder cancer: A prospective study

Background: Intravesical Bacille Calmette-Guérin (BCG) immunotherapy has been used for several decades as a prophylactic approach against recurrence of superficial bladder cancer. However, its effectiveness has been both variable and unpredictable. Typically, cancer BCG-immunotherapy aims to redirect or modulate both innate and adaptive immune responses. The consequences of gene polymorphisms in several key immuno-regulatory molecules on the heterogeneity of the response to BCG-immunotherapy have been investigated.Objective: The aim of this study was to evaluate the association of toll-like receptor (TLR) 2 polymorphisms (arginine to glutamine substitution at position 753 [Arg753Gln] and arginine to tryptophan substitution at position 677 [Arg677Trp]) and the outcome of BCG-immunotherapy.Methods: This prospective study was conducted during a 3-year period from June 2006 to July 2009. Consecutive patients were recruited during a 1-year period and followed for 2 years at the Department of Urology, Charles Nicolle Hospital, Tunis, Tunisia. Patients with superficial bladder tumors at stage Ta (noninvasive papillary carcinoma) or T1 (where the tumor has grown from the layer of cells lining the bladder into the connective tissue below but has not grown into the muscle layer of the bladder) of any grade were eligible; carcinoma in situ cases were excluded. The TLR2 Arg753Gln and Arg677Trp polymorphisms were studied in peripheral blood DNA from patients treated with BCG-immunotherapy after transurethral resection.Results: A total of 112 consecutive patients were enrolled (101 men and 11 women; mean age, 63.9 years [range, 25–85 years]) and completed the 2-year followup. Polymerase chain reaction amplification followed by direct sequencing of the region containing the TLR2 single-nucleotide polymorphism (SNP) of interest did not detect Arg753Gln or Arg677Trp in any of the study participants belonging to either of 2 groups: responders (n = 67) and nonresponders (n = 45) to BCG-immunotherapy.Conclusions: No patients included in the study were found to have the 2 known TLR2 nonsynonymous SNPs, and the relative importance of these polymorphisms could not be definitely determined. However, a significant proportion of patients without these polymorphisms responded to BCG-immunotherapy, suggesting that these genetic variants are not critical in the effectiveness of this approach for preventing recurrence of the tumor.