Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

Abstract

We found a significant correlation between lung cancer in smokers and the expression of a human gene, D40, predominantly expressed in testis and cancers. In an attempt to clone a novel human gene, we screened a cDNA library derived from a human B cell line and obtained a cDNA clone that we refer to as D40. A search for public databases for sequence homologies showed that the D40 gene is identical to AF15q14. D40 mRNA is predominantly expressed in normal testis tissue. However, this gene is also expressed in various human tumour cell lines and primary tumours derived from various organs and tissues, such as lung cancer. We examined the relationship between D40 expression and clinico-pathological characteristics of tumours in primary lung cancer. D40 expression did not significantly correlate with either histological type or pathological tumour stage. However, D40 expression was observed more frequently in poorly differentiated tumours than in well or moderately differentiated ones. Furthermore, the incidence of D40 expression was significantly higher in tumours from patients who smoke than in those from non-smokers. D40/AF15q14 is the first gene in the cancer/testis family for which expression is related to the smoking habits of cancer patients.

The protein encoded by cancer/testis gene D40/AF15q14 is localized in spermatocytes, acrosomes of spermatids and ejaculated spermatozoa

“…Poorly differentiated lung tumors express D40 more frequently than wellor moderately differentiated ones. In addition, the incidence of D40 expression was significantly higher in tumors from patients who smoke than in those from nonsmokers (Takimoto et al 2002).…”

“…Previously, we have cloned and reported a human gene, D40, a new cancer/testis gene (Wei et al 1999, Takimoto et al 2002. This gene is expressed predominantly in testis among normal organs and tissues, while it is widely expressed in a variety of cultured human cancer cell lines and primary tumors derived from various tissues and organs.…”

“…MLL gene is often activated by chromosomal translocation in human leukemias (Ayton & Cleary 2001). The function of the D40/AF15q14 gene is elusive, as there is no domain with known function except for a potential nuclear localization signal (Hayette et al 2000, Takimoto et al 2002, Kuefer et al 2003.…”

Sperm-associated antigen 1 is expressed early in pancreatic tumorigenesis and promotes motility of cancer cells

“…Pancreatic CT genes are among the least studied; the latest report of Kubuschok et al (2004) shows that out of 10 different CT genes analysed, only HOM-TES-14/ SCP-1 and GAGE were expressed in a significant proportion of pancreatic tumour cases (48 and 21%, respectively), SCP-1 (synaptonemal complex protein) is expressed in almost 50% of PDAC specimens (Tureci et al, 1998), whereas D40/CT29 was found expressed in not more than 27% of PDACs (Takimoto et al, 2002). Except for SCP-1, which plays an important role in the alignment of the two homologous chromosomes, in promoting crossing-over events and ensuring chromosome segregation in meiosis (Tureci et al, 1998), the function of the remaining CT genes is completely unknown.…”

Expression of multiple epigenetically regulated cancer/germline genes in nonsmall cell lung cancer

“…[22][23][24][25][26] However, investigations encompassing more recently described members of this class and studies addressing the cumulative expression of a set of several CG genes are not available yet. Moreover, previous studies have not correlated CG gene expression to the histological subtype of lung cancer.…”