Familial Cancer Associated with a Polymorphism inARLTS1

Abstract

A genetic variant of ARLTS1 predisposes patients to familial cancer.

The 13q and 11q B‐cell chronic lymphocytic leukaemia‐associated regions derive from a common ancestral region in the zebrafish

“…Recently the human ARLTS1 gene within the minimal 13q14-deleted region was described as a tumour suppressor gene in familial CLL (Calin et al, 2005b). hsa-mir-34b-2 hsa-mir-34c…”

MicroRNAs and chromosomal abnormalities in cancer cells

“…Further detailed investigation showed that both genes are deleted or downregulated in approximately 68% of CLL cases as compared with CD5 þ lymphocytes from healthy donors (Calin et al, 2002). Furthermore, a rare mutation identified in two CLL patients including one from a family with individuals having CLL and breast cancer, and possibly affecting the expression of these genes was found to be associated with the loss of the normal allele in the leukemic cells (Calin et al, 2005a). Fully explaining the tumor-suppressor function of miR-15 and miR-16, it was proved that the levels of both genes inversely correlates with the BCL2 protein expression, and that BCL2 repression by miR-15a and miR-16-1 induces apoptopsis in leukemia cells (Cimmino et al, 2005).…”

“…Until year 2001, a total of eleven genes have been identified and screened for alterations at the DNA and/or RNA level in sporadic and familial cases of CLL. However, detailed genetic analysis, including extensive LOH, mutation and expression studies, failed to demonstrate the consistent involvement of any of the genes located in the deleted region (described in Calin et al (2005c) and Migliazza et al (2001)). …”

“…The dimensions of miRNAs are quite small in respect with the cDNAs of protein coding genes, and therefore the mutations in miRNA transcripts should be rare events. A combination of LOH þ mutation was reported as inactivating 'two-hit' events in two cases of CLL (Calin et al, 2005a), while a naturally occurring sequence polymorphism in an miRNA precursor that results in reduced processing and lower levels of mature miRNA expression and function has been reported (Gottwein et al, 2006). An independent study on human cancer cell lines showed that heterozygous genetic variants in miRNA precursors are common, but are unlikely to have physiologic significance (Diederichs and Haber, 2006).…”

“…Bold represents statistically significant P-values. After the identification of specific miRNA signatures in CLL (Calin et al, 2004a(Calin et al, , 2005a, miRNAs differentially expressed between tumors and normal counterparts were identified for several tumor types like lymphoma (He et al, 2005b), breast cancer , lung cancer (Yanaihara et al, 2006), thyroid papillary carcinoma (He et al, 2005a), glioblastoma (Ciafre et al, 2005), hepatocellular carcinoma (Murakami et al, 2006), colorectal carcinoma (Cummins et al, 2006) and pancreatic tumors (Roldo et al, 2006).…”