We report the case of a 21-year-old girl who presented an eyelid tumor with retinal hamartoma. General examination revealed a basal cell nevus on the face, jaw cysts, skeletal malformations and brain calcifications. Histological examination of the eyelid lesion and of the skin nevus showed basal cell carcinoma. Familial investigation evidenced the hereditary nature of this disease. We review Gorlin-Goltz phakomatosis, an uncommon disease often unrecognized by ophthalmologists, and discuss nosological considerations.

Gardner syndrome is a type of hereditary gastrointestinal polyposis. Dental professionals should be aware that this syndrome can present as multiple impacted teeth and sometimes as large osteomas in the head and neck area. Following a brief review of literature, we present two cases of Gardner syndrome. One of these cases was diagnosed after a dental examination. The high incidence of malignant transformation of polyps into colorectal cancer indicates the importance of early diagnosis and follow-up.

Human papillomaviruses (HPVs) are associated with a broad spectrum of cutaneous and mucosal lesions. Until now, more than 120 genotypes have been identified. Most HPVs are associated with benign lesions. Nevertheless certain HPV types are frequently found in carcinomas. For instance, HPV 16 and 18 which are frequently associated with cervical cancer, are capable of immortalizing and transforming primary keratinocytes. The mechanism of transformation is linked to the viral genome integration into the cell's DNA, accompanied by an overexpression of the E6 and E7 genes. The viral gene products interact with cellular proteins that regulate the cycle progression. In particular, the E6 protein binds to the p53 and the E7 protein binds to the p105(Rb). The inactivation of both cellular proteins distorts the cell cycle and results in genetic instability and cellular gene alterations. This article reviews the role of the viruses in the carcinogenesis, the genome structure and the gene expression of HPVs. It also addresses the cell cycle regulation with a focus on the role of HPVs in cell transformation.

This study reviews different aspects of hereditary colorectal cancer associated with three polyposis syndromes: familial adenomatous polyposis, juvenile polyposis coli and Peutz-Jeghers syndrome. All these syndromes share some similarities: low incidence, autosomal dominant inheritance, genetic predisposition to colorectal cancer and/or other extracolonic cancers. Classical familial adenomatous polyposis is clinically defined by the presence of hundreds of adenomatous polyps in the colon and rectum, whereas less than 100 polyps are found in attenuated familial adenomatous polyposis. Without prophylactic colectomy, colorectal cancer develops inevitably by the age of 40. Restorative proctocolectomy with ileal anal-pouch anastomosis is the operation of choice in familial adenomatous polyposis. In juvenile polyposis coli, 50-200 hamartomatous polyps are found in the colon, rectum, stomach and small bowel. Life-time cumulative risk for colorectal cancer is estimated to be 50%. Prophylactic colectomy is required only in cases in which endoscopic surveillance is not able to control polyp development. Hereditary mixed polyposis syndrome is a variant form of juvenile polyposis coli, consisting of multiple mixed adenomatous, hyperplastic and hamartomatous polyps. Peutz-Jeghers syndrome is characterized by multiple hamartomatous polyps located in the small bowel, colon and stomach. Small bowel follow through and colonoscopy is advised for surveillance. Surgery is warranted only in cases of polyps larger than 1 cm. The causative genes of these syndromes have been cloned. Molecular genetic testing of affected and at-risk individuals is proposed in order to advise surveillance and management.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant condition in which affected individuals develop colorectal cancer or extracolonic cancer, most commonly endometrial, at an early age. Recent advances in molecular genetics have led to the identification of a germline mutation of DNA mismatch-repair genes to be responsible for the majority of HNPPC cases. Since clinical screening of gene carriers can help to prevent cancer, it is important to devise strategies applicable to this syndrome. Recommendations for current management, especially screening and surgical treatment are under study, as they have not yet been clearly established. This paper reviews the clinical presentation, the molecular genetic diagnosis and therapeutic approaches of this syndrome including the controversies concerning prophylactic colectomy for cancer or gene carriers.

T-prolymphocytic leukemia (T-PLL) is a rare form of mature T-cell leukemia associated with chromosomal rearrangements of band 14q11, containing the gene TCRA/D, and bands 14q32.1 and Xq28, where the TCL1 and MTCP1 putative oncogenes have been identified. These genes encode two homologous proteins, p14(TCL1) and p13(MTCP1) respectively, which share no similarity with other known proteins. To determine the oncogenic role of MTCP1, transgenic mice with an expression of MTCP1 targetted to the T-cells were generated. A lymphoïd malignancy similar to Human T-PLL occurred in to independent transgenic lines with a high level of expression of the transgene. The cumulative incidence of the disease at 20 months was 100% and 50% respectively, and null in the control group. The oncogenic role of MTCP1 is demonstrated, and the p13(MTCP1) and p14(TCL1) proteins form a new oncoprotein family. The long latency period before emergence of tumors suggests that activation of MTCP1 is not sufficient to generate the malignant transformation. The secondary genetic events implicated in tumoral progression remain to be elucidated, in order to reconstruct the molecular history of the disease.

The genotype-phenotype relationship of Lynch syndrome displays many enigmatic features which cannot be explained satisfactorily by the prevailing concepts of carcinogenesis and genetic predisposition to cancer. We propose here a new model of carcinogenesis divided into two and only two evolutive phases: a) a preliminary phase starting with the counter-selective loss of mismatch repair function, in which most clones with the RER mutator phenotype are eliminated through apoptosis or an accelerated ageing process; b) an explosive phase that is initiated only if mutations blocking apoptosis and senescence, rapidly acquired during the short life span of the non-transformed RER+ clones, eventually rescue one mismatch repair-deficient cell that gives rise to the malignant clone. Carcinogenesis is proposed here to progress irreversibly and very rapidly once initiated. We shall show how this model provides a meaningful etiologic and pathogenic interpretation of all the curious features of Lynch syndrome.

Chromosomal deletions are the most frequent genetic alterations observed in hepatocellular carcinoma. Loss of heterozygosity on chromosome 4q has been observed in 40% of hepatocellular carcinomas suggesting the presence of a tumor suppressor gene which has not yet been identified.