Infrequent Genetic Alterations of the PTEN/MMAC1 Gene in Japanese Patients with Primary Cancers of the Breast, Lung, Pancreas, Kidney, and Ovary

Abstract

In the present study, we searched for genetic alterations of the entire coding region of PTEN/MMACl, a recently isolated candidate tumor suppressor gene, in 178 specimens from Japanese patients with various malignant tumors by the polymerase chain reaction‐single strand conformation polymorphism method. The samples consisted of 11 glioblastoma multiformes (GBMs), 14 astrocytomas, 47 breast cancers, 25 non‐small cell lung cancers, 9 small cell lung cancers, 8 pancreatic cancers, 24 renal cell carcinomas, 20 ovarian cancers, and 20 metastatic lung tumors from various organs. Only one somatic frameshift mutation at codon 319 was observed in one (9%) of eleven GBMs. Our results suggest that mutation of the PTEN/MMAC1 gene does not play a major role in carcinogenesis, at least in the tumor types from Japanese patients analyzed in this study.

Intragenic PTEN/MMAC1 Loss of Heterozygosity in Conventional (Clear-Cell) Renal Cell Carcinoma is Associated with Poor Patient Prognosis

“…While Steck et al (11) reported mutations in one of four primary renal carcinomas, later, larger studies have found no, or very few, PTEN/MMAC1 mutations in RCC (13)(14)(15)(16)(17). Furthermore, observations in other human tumor types have also shown few PTEN/MMAC1 mutations despite high LOH rates at the gene locus (22,23).…”

“…Initial screens of 9 RCCs seemed to support this hypothesis, showing loss of heterozygosity (LOH) in 40% of tumors and mutations in 15% of tumors (11,12). However, two subsequent larger studies failed to detect any mutations (13,14). Recently, Alimov et al (15) reported a 34% LOH rate at 10q23-25 but found only three mutations when they screened the subset of tumors that displayed LOH for mutations; Kondo et al (16) detected only five mutations, some of which were heterozygote, in a series of 68 sporadic renal cell carcinomas; and Sukosd et al (17) found high rates of 10q23.3 LOH in chRCC, but only in 2 of 50 cRCC, and detected no PTEN/MMAC1 mutations in the tumors with LOH.…”

Reduced PTEN expression in the pancreas overexpressing transforming growth factor-beta 1

“…In this study we found significantly decreased levels of PTEN mRNA in pancreatic cancers. Since two reports have demonstrated that PTEN mutations or deletions are not present in pancreatic cancers (Sakurada et al, 1997;Okami et al, 1998), other molecular mechanisms must contribute to its altered expression in pancreatic cancer. In a study by Li et al (1997a) the protein tyrosine phosphatase PTEN was found to be rapidly down-regulated by TGF-b1 in the HaCaT keratinocyte cell line.…”

“…Cowden Disease and the Bannayan-Zonana-syndrome, point to a role of PTEN as a tumour suppressor gene in the pathogenesis of malignant tumours. However, PTEN mutations or deletions do not seem to be present in pancreatic cancer (Sakurada et al, 1997;Okami et al, 1998). Since PTEN expression is regulated by TGF-b1 (Li et al, 1997a), we assessed PTEN mRNA levels in human pancreatic cancers by RT -PCR analysis and immunohistochemistry.…”

Mutation in the PTEN/MMAC1 gene in archival low grade and high grade gliomas

“…LOH at the PTEN locus and mutations in the PTEN gene have been reported in a wide variety of sporadic cancers, including prostate Suzuki et al, 1998), primary breast tumours (Rhei et al, 1997), malignant melanomas (Guldberg et al, 1997) and endometrial carcinomas (Tashiro et al, 1997;Risinger et al, 1997). In the gliomas investigated so far, 16% of anaplastic astrocytomas and 26% of glioblastomas had PTEN mutations, but none have been found in low grade gliomas Liu et al, 1997;Rasheed et al, 1997;Sakurada et al, 1997;Steck et al, 1997;Wang et al, 1997;Böstrom et al, 1998;Chiariello et al, 1998). Thus, genetic alterations in the PTEN gene may be involved in the progression of gliomas to advanced disease.…”