http://www.hccpjournal.com The latest research articles published by Hereditary Cancer in Clinical Practice 2013-04-01T00:00:00Z The history of specific therapy for hereditary tumors dates back to mid 1980s and involves a number of reports demonstrating regression of familial colon polyps upon administration of sulindac. Virtually no clinical studies on other hereditary cancer types were available until the year 2009, when Byrski et al. presented the data on unprecedented sensitivity of BRCA1-associated breast malignancies to cisplatin. This breakthrough has revived interest to the treatment of cancer in germ-line mutation carriers. Recent trials and clinical observations have confirmed the efficacy of platinating agents and PARP inhibitors in BRCA1/2-driven breast, ovarian and pancreatic carcinomas. Pegylated liposomal doxorubicin may be considered as a promising treatment option for BRCA1/2-related ovarian cancer after the failure of platinum-containing therapy. Several novel drugs have been recently introduced in the management of rare familial tumor syndromes. Vandetanib, a low-molecular weight RET kinase inhibitor, demonstrated substantial efficacy in the treatment of hereditary and sporadic medullary thyroid cancer. Vismodegib, an inhibitor of SMO oncoprotein, caused regression of basal-cell carcinomas in patients with Gorlin syndrome. Down-regulation of mTOR kinase by everolimus has been successfully used for the therapy of subependymal giant-cell astrocytomas in patients with tuberous sclerosis. The achievements in the prevention, diagnostics and treatment of hereditary cancers may serve as an excellent example of triumph of translational medicine. http://www.hccpjournal.com/content/11/1/2 Evgeny Imyanitov Tomasz Byrski Hereditary Cancer in Clinical Practice 2013, null:2 2013-04-01T00:00:00Z doi:10.1186/1897-4287-11-2 /content/figures/1897-4287-11-2-toc.gif Hereditary Cancer in Clinical Practice 1897-4287 ${item.volume} 2 2013-04-01T00:00:00Z XML Background: Family history is among the few established risk factors for testicular germ cell tumor (TGCT). Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to six fold and eight- to tenfold increase in TGCT risk, respectively. In twins of men with TGCT the relative risk of testicular cancer is 37.5 (12.3-115.6). Nevertheless, information about the occurrence of TGCT in relatives of patients with extragonadal germ cell tumor is limited.Case reportA 24 year-old male patient was diagnosed with a mediastinum tumor and was submitted to image-guided biopsy, which revealed a seminoma. Two months later, his non-identical asymptomatic twin brother was submitted to an elective ultrasound of the testes, which showed a left testicular mass of 4.2 cm. This patient underwent orchiectomy revealing a seminoma of the left testis. There are no other cases of seminoma or other types of cancers reported in first-degree relatives in this family. Conclusions: Although familial aggregations of TGCT have been well described, to the best of our knowledge, no data concerning the association of gonadal and extragonadal germ cell tumor in relatives has been previously reported. Further investigation on this association is warranted and may help in improving our knowledge of familial pattern inheritance. http://www.hccpjournal.com/content/11/1/1 Rodrigo Santa Cruz Guindalini Edite Paulo de Oliveira Marina Cavalcanto Moroja Silvino Paulo Marcelo Hoff Bernardo Garicochea Hereditary Cancer in Clinical Practice 2013, null:1 2013-03-04T00:00:00Z doi:10.1186/1897-4287-11-1 /content/figures/1897-4287-11-1-toc.gif Hereditary Cancer in Clinical Practice 1897-4287 ${item.volume} 1 2013-03-04T00:00:00Z XML Worldwide, gastric cancer is one of the most common forms of cancer, with a high morbidity and mortality. Several environmental factors predispose to the development of gastric cancer, such as Helicobacter pylori infection, diet and smoking. Familial clustering of gastric cancer is seen in 10% of cases, and approximately 3% of gastric cancer cases arise in the setting of hereditary diffuse gastric cancer (HDGC). In families with HDGC, gastric cancer presents at relatively young age. Germline mutations in the CDH1 gene are the major cause of HDGC and are identified in approximately 25-50% of families which fulfill strict criteria. Prophylactic gastrectomy is the only option to prevent gastric cancer in individuals with a CDH1 mutation. However, in the majority of families with multiple cases of gastric cancer no germline genetic abnormality can be identified and therefore preventive measures are not available, except for general lifestyle advice. Future research should focus on identifying new genetic predisposing factors for all types of familial gastric cancer. http://www.hccpjournal.com/content/10/1/18 Ingrid Vogelaar Rachel van der Post Tanya Bisseling J Han van Krieken Marjolijn Ligtenberg Nicoline Hoogerbrugge Hereditary Cancer in Clinical Practice 2012, null:18 2012-12-12T00:00:00Z doi:10.1186/1897-4287-10-18 /content/figures/1897-4287-10-18-toc.gif Hereditary Cancer in Clinical Practice 1897-4287 ${item.volume} 18 2012-12-12T00:00:00Z XML During the past decade many new molecular methods for DNA and RNA analysis have emerged. The most popular thus far have been SSCP, HET, CMC, DGGE, RFLP or ASA, which have now been replaced by methods that are more cost effective and less time consuming. Real-time amplification techniques and particularly those with the capacity of multiplexing have become commonly used in laboratory practice. Novel screening methods enable the very rapid examination of large patients series. Use of liquid handling robotics applied to the isolation of DNA or RNA, the normalisation of sample concentration, and standardization of target amplification by PCR have also contributed to a reduced risk of sample contamination and have resulted in laboratory analysis being easier and faster.The aim of this study is the introduction of a few modern techniques, most commonly used in detection of genetic predisposition to cancer. http://www.hccpjournal.com/content/10/1/17 Grzegorz Kurzawski Dagmara Dymerska Pablo Serrano-Fernández Joanna Trubicka Bart¿omiej Masoj¿ Anna Jakubowska Rodney Scott Hereditary Cancer in Clinical Practice 2012, null:17 2012-12-04T00:00:00Z doi:10.1186/1897-4287-10-17 /content/figures/1897-4287-10-17-toc.gif Hereditary Cancer in Clinical Practice 1897-4287 ${item.volume} 17 2012-12-04T00:00:00Z XML Background: Chemokine and chemokine receptors play an essential role in tumorigenesis. Although chemokine-associated single nucleotide polymorphisms (SNPs) are associated with various cancers, their impact on prostate cancer (PCA) among men of African descent is unknown. Consequently, this study evaluated 43 chemokine-associated SNPs in relation to PCA risk. We hypothesized inheritance of variant chemokine-associated alleles may lead to alterations in PCA susceptibility, presumably due to variations in antitumor immune responses. Methods: Sequence variants were evaluated in germ-line DNA samples from 814 African-American and Jamaican men (279 PCA cases and 535 controls) using Illumina’s Goldengate genotyping system. Results: Inheritance of CCL5 rs2107538 (AA, GA+AA) and rs3817655 (AA, AG, AG+AA) genotypes were linked with a 34-48% reduction in PCA risk. Additionally, the recessive and dominant models for CCR5 rs1799988 and CCR7 rs3136685 were associated with a 1.52-1.73 fold increase in PCA risk. Upon stratification, only CCL5 rs3817655 and CCR7 rs3136685 remained significant for the Jamaican and U.S. subgroups, respectively. Conclusions: In summary, CCL5 (rs2107538, rs3817655) and CCR5 (rs1799988) sequence variants significantly modified PCA susceptibility among men of African descent, even after adjusting for age and multiple comparisons. Our findings are only suggestive and require further evaluation and validation in relation to prostate cancer risk and ultimately disease progression, biochemical/disease recurrence and mortality in larger high-risk subgroups. Such efforts will help to identify genetic markers capable of explaining disproportionately high prostate cancer incidence, mortality, and morbidity rates among men of African descent. http://www.hccpjournal.com/content/10/1/16 LaCreis Kidd Dominique Jones Erica Rogers Nayla Kidd Sydney Beache James Rudd Camille Ragin Maria Jackson Norma McFarlane-Anderson Marshall Tulloch-Reid Seian Morrison Guy Brock Shirish Barve Kevin Kimbro Hereditary Cancer in Clinical Practice 2012, null:16 2012-11-20T00:00:00Z doi:10.1186/1897-4287-10-16 /content/figures/1897-4287-10-16-toc.gif Hereditary Cancer in Clinical Practice 1897-4287 ${item.volume} 16 2012-11-20T00:00:00Z XML Café au lait spots (CALS) are common dermatologic findings that can at the same time arise in a variety of pathologic conditions such as Neurofibromatosis type 1 (NF1), together with numerous hereditary syndromes for which they represent either diagnostic criteria or associated elements (McCune Albright, Silver-Russell, LEOPARD, Ataxia-Telangiectasia). A review of the literature also revealed two cases of association with NBCCS. We report here the case of a female proband with CALS associated to Nevoid Basal Cell Carcinoma Syndrome (NBCCS) with known PTCH1 germline mutation (C.1348-2A>G) who had been misdiagnosed with NF1 in her childhood because of 5 CALS and cutaneous nodules. The patient presented a giant cell tumor of the skin, palmar and calcaneal epidermoidal cystic nodules, odontogenic keratocystic tumors and deformity of the jaw profile. Her family history brought both her brother and father to our attention because of the presence of KCOTs diagnosed at early age: after genetic testing, the same PTCH1 germline mutation was identified in the three family members. Clinical criteria are used for discerning NF1 diagnosis (size, number and onset age), while there are no definite guidelines concerning CALS except for their presence. In our experience, we have noted an association of CALS with NBCCS; this seems interesting because we already know clinical criteria are a dynamic entity and can be modified by epidemiologic evidences. http://www.hccpjournal.com/content/10/1/15 Giovanni Ponti Aldo Tomasi Lorenza Pastorino Cristel Ruini Carmelo Guarneri Victor Mandel Stefania Seidenari Giovanni Pellacani Hereditary Cancer in Clinical Practice 2012, null:15 2012-10-29T00:00:00Z doi:10.1186/1897-4287-10-15 /content/figures/1897-4287-10-15-toc.gif Hereditary Cancer in Clinical Practice 1897-4287 ${item.volume} 15 2012-10-29T00:00:00Z XML The mutations of the RET proto-oncogene contributes to the development of MTC by increasing the activity of the receptor encoded by this gene. Variant T of polymorphism rs2435357 located in the enhancer of the RET gene reduces the enhancer’s activity. The opposite effects of rs2435357 and the mutations causing medullary thyroid carcinoma resulted in the investigation of the status of this polymorphism in patients with MTC. In our study, we compared the frequency of polymorphism rs2435357 in the group of 48 MTC patients with its frequency in Polish population. The frequency of heterozygotes C/T at rs2435357 reached almost 12% (18/152) for the Polish population, in contrast to the group of MTC patients where not even a single T allele was found. The frequency difference is statistically significant. This observation might indicate that the presence of the heterozygous T allele at rs2435357 may be associated with the inhibition of medullary thyroid carcinoma development. http://www.hccpjournal.com/content/10/1/14 Pawel Borun Sowinski Jerzy Katarzyna Ziemnicka Lukasz Kubaszewski Daniel Lipinski Andrzej Plawski Hereditary Cancer in Clinical Practice 2012, null:14 2012-10-22T00:00:00Z doi:10.1186/1897-4287-10-14 /content/figures/1897-4287-10-14-toc.gif Hereditary Cancer in Clinical Practice 1897-4287 ${item.volume} 14 2012-10-22T00:00:00Z XML Mutations in FLCN cause Birt-Hogg-Dubé syndrome, an autosomal dominant disorder notable for development of cutaneous fibrofolliculomas or trichodiscomas, a variety of renal tumors, and spontaneous pneumothorax due to cystic lung changes. We present a woman referred for genetic evaluation due to bilateral parotid gland tumors, who was subsequently diagnosed with Birt-Hogg-Dubé syndrome. http://www.hccpjournal.com/content/10/1/13 Noralane Lindor Jan Kasperbauer Jean Lewis Mark Pittelkow Hereditary Cancer in Clinical Practice 2012, null:13 2012-10-10T00:00:00Z doi:10.1186/1897-4287-10-13 /content/figures/1897-4287-10-13-toc.gif Hereditary Cancer in Clinical Practice 1897-4287 ${item.volume} 13 2012-10-10T00:00:00Z XML Paragangliomas are rare tumours with a prevalence of 1/10000 to 1/30000. Tumors arising from the paraganglia are characteristically of low malignant potential. Vertebral metastases are exceedingly rare, and only isolated case reports have described them. The authors present the clinical course of a 47 years-old female patient with a familial paraganglioma [PGL] with vertebral metastastization, who underwent an intralesional tumor excision and corpectomy. Genetic screening demonstrated a new germinal frameshift mutation of the SDHB exon 6 [c.587-591DelC]. After surgery there was normalization of the analytical parameters and imagiologic screening. One year later she presented a new image in the the pedicle of T11 on the contralateral side of the surgical incision. She performed 2 treatments with MIBG and 1 cicle of radiotherapy that made the new lesion regress. Currently the patient does not present any clinical or analytical evidence of new metastasis.This case outlines the clinical course of a patient with a PGL syndrome for whom a rare vertebral metastasis was diagnosed. It highlights the importance of identifying patients with germline SDHB mutations, as these patients are at a high risk of developing malignant disease. http://www.hccpjournal.com/content/10/1/12 Manuel Ribeiro da Silva Manuel Santos Carvalho Pedro Cacho Rodrigues Nuno Neves Antonio Moura Gonçalves Rui Pinto Davide Carvalho Hereditary Cancer in Clinical Practice 2012, null:12 2012-09-21T00:00:00Z doi:10.1186/1897-4287-10-12 /content/figures/1897-4287-10-12-toc.gif Hereditary Cancer in Clinical Practice 1897-4287 ${item.volume} 12 2012-09-21T00:00:00Z XML Background: Cyclin-dependent kinase 4 (CDK4) together with its regulatory subunit cyclin D1, governs cell cycle progression through G1 phase. Cyclin-dependent kinase inhibitors, including p16INK4A in turn regulate CDK4. In particular, deregulation of the p16/CDK4/cyclin D1 complex has been established in a variety of human tumors including gliomas, sarcomas, melanoma, breast and colorectal cancer. However, changes in CDK4 have rarely been observed.MethodIn this study we used a combination of PCR-SSCP and direct sequencing for mutational screening of CDK4. DNA was isolated from peripheral blood leukocyte of patients with squamous cell carcinoma of head and neck, for screening germline mutations in coding regions of CDK4. Results: Variations observed in exon 2 and 5 were three missense mutations, g5051G > C (Ser52Thr), g5095G > C (Glu67Gln), g5906C > A, g5907C > G (Pro194Ser) and novel frame shift mutations g7321_23delTGA, g7121_7122insG, g7143delG in exon 7 and 3′UTR respectively. Conclusion: In conclusion, two novel mutations were found in N terminal domain which indicates that CDK4 mutation may play a major role in the development and progression of squamous cell carcinoma of head and neck. http://www.hccpjournal.com/content/10/1/11 Maimoona Sabir Ruqia baig Ishrat mahjabeen Mahmood Kayani Hereditary Cancer in Clinical Practice 2012, null:11 2012-08-29T00:00:00Z doi:10.1186/1897-4287-10-11 /content/figures/1897-4287-10-11-toc.gif Hereditary Cancer in Clinical Practice 1897-4287 ${item.volume} 11 2012-08-29T00:00:00Z XML