Identification of two distinct tumor-suppressor loci on the long arm of chromosome 10 in small cell lung cancer

Kim, Se K.; Ro, Jae Y.; Kemp, Bonnie L.; Lee, Jin Soo; Kwon, Tae J.; Hong, Waun Ki; Li, Mao

doi:10.1038/sj.onc.1202073

Cited by 77 publications

(78 citation statements)

References 20 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In an e ort to ®nd a molecular correlate for the markedly malignant phenotype of SCLC, genetic alterations and abnormal expression patterns of many oncogenes and tumor suppressor genes have been investigated. Multiple chromosomal deletions on 3p, 4q, 5q, 9p, 10q, 13q and 17p as well as DNA over-representations on 3q and 5p have been found in primary tumors and their metastases (Kim et al, 1997;Petersen et al, 1997;Cook et al, 1993). Several tumor suppressor genes have been found to be altered frequently in SCLC including RB whose protein expression is absent or truncated in the majority of tumors and cell lines and p53 which is mutated in more than 80% of tumors and cell lines (Harbour et al, 1988;Rygaard et al, 1992;D'Amico et al, 1992;Miller et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

TSG101 is not mutated in lung cancer but a shortened transcript is frequently expressed in small cell lung cancer

Proctor

Fan

et al. 1998

Oncogene

Self Cite

View full text Add to dashboard Cite

TSG101 is a candidate tumor suppressor gene whose deletion in NIH3T3 cells leads to spontaneous lung metastases in nude mice. Aberrant transcripts of TSG101 have been identi®ed in 47% of primary breast carcinomas, without evidence of intragenic deletions at the TSG101 locus on 11p15. To investigate the possible role of TSG101 in lung cancer, which often shows 11p allele loss, we performed transcript analysis and mutational analysis of TSG101 in lung cancer cell lines. Reverse transcriptase RT ± PCR and Northern analysis detected a common TSG101 transcript, shortened because of an internal deletion, which was expressed simultaneously with the wild-type transcript in 89% of small cell lung cancer (SCLC) lines. In contrast, the wild-type transcript was expressed alone in normal tissues, primary non-small cell lung cancer (NSCLC) specimens, and the majority of NSCLC cell lines. Sequence of the shortened SCLC transcript was identical to that of the most common aberrant transcript identi®ed in breast cancer, consisting of a deletion of exons 2 ± 4 and part of 1 and 5. Southern analysis of SCLC lines expressing the shortened transcript did not detect any intragenic deletions. Single strand conformational polymorphism (SSCP) analysis and direct sequencing of TSG101 cDNAs also identi®ed no mutations or deletions. These results suggest that TSG101 is not mutated in lung cancer but that aberrant splicing of TSG101 occurs in SCLC.

show abstract

Section: Introductionmentioning

confidence: 99%

TSG101 is not mutated in lung cancer but a shortened transcript is frequently expressed in small cell lung cancer

Proctor

Fan

et al. 1998

Oncogene

Self Cite

View full text Add to dashboard Cite

show abstract

“…In fact, many lung cancers may have lost a whole chromosome 9 (Merlo et al, 1994a and1994b). Our recent study revealed at least three distinct minimally deleted regions at 9p in SCLCs (Kim et al, 1997), and one of the regions is close to the region of the PTH2 gene. LOH analysis of primary SCLCs using extensive microsatellite markers close to PTH2 should provide further information.…”

Section: Discussionmentioning

confidence: 78%

“…The short arm of chromosome 9 is frequently deleted in many types of human cancer, including SCLC and non-small cell lung cancer (NSCLC) (Kim et al, 1997;Merlo et al, 1994a, b). Although the p16 tumor suppressor gene located at 9p21 is inactivated in many human cancers (Nobori et al, 1994;Kamb et al, 1994;Merlo et al, 1995;Cairns et al, 1995), the presence of other tumor suppressor genes in chromosome 9 has been suggested (Kim et al, 1997;Ohta et al, 1996b;Wiest et al, 1997). In fact, many lung cancers may have lost a whole chromosome 9 (Merlo et al, 1994a and1994b).…”

Section: Discussionmentioning

confidence: 99%

“…However, other potential tumor suppressor genes that may play roles in SCLC have not yet been found. For example, 9p is one of the most frequently deleted chromosome arms in SCLC (Kim et al, 1997), and alterations of p16 gene (9p21), which is inactivated frequently in many tumor types, are not often observed in SCLC (Otterson et al, 1994;Kelley et al, 1995), suggesting the presence of other yet to be identi®ed tumor suppressor genes on 9p.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines

Kim

et al. 1998

Oncogene

Self Cite

View full text Add to dashboard Cite

Loss of heterozygosity (LOH) at chromosome 10q23-q25 is frequent in small cell lung cancer (SCLC), indicating the presence of putative tumor suppressor genes. PTEN/ MMAC1, a newly cloned candidate tumor suppressor gene at 10q23, was mutated in multiple human cancers. We investigated whether mutations of PTEN/MMAC1 play an important role in SCLC tumorigenesis. We examined 16 SCLC cell lines for PTEN/MMAC1 mRNA expression by reverse-transcriptase polymerase chain reaction (RT ± PCR) and potential mutations by sequencing analysis of the PTEN/MMAC1 coding region. No mutation was observed in PTEN/MMAC1 cDNAs in 15 cell lines expressing PTEN/MMAC1. One SCLC cell line, DMS79, did not have detectable PTEN/ MMAC1 expression. Importantly, we identi®ed a novel homologue of PTEN/MMAC1, termed PTH2, localized to chromosome 9p21-q13 and containing only ten amino acid substitutions compared with the PTEN/MMAC1 coding region. However, because the putative initiation codon for PTEN/MMAC1 gene was changed to arginine in PTH2, the translational initiation site of PTH2 is very likely to di er from that of the PTEN/MMAC1. PTH2 was expressed in two normal lung tissues and two normal colon tissues, but in only four of 16 SCLC cell lines. A missense mutation in PTH2 was identi®ed in a SCLC cell line that did not express PTEN/MMAC1 mRNA. Our data suggest that inactivation of PTEN/ MMAC1 is a rare event in SCLC tumorigenesis. However, the PTEN/MMAC1 homologue PTH2 may play a role in SCLC tumorigenesis.

show abstract

“…10 More than 89% of lung tumors were found to exhibit loss of heterozygosity on 9p, with 3 distinct deleted areas, suggesting the presence of at least 3 novel tumor suppressor loci on 9p in SCLC. 11 Several well-characterized tumor suppressor genes (TSGs), including p16/ CDKN2, MTAP, P16␤ and p15, have been mapped to 9p. In addition, the new putative tumor suppressor gene TSC1, mapped to 9q, might be involved in lung adenocarcinoma.…”

mentioning

confidence: 99%

A case‐control analysis of lymphocytic chromosome 9 aberrations in lung cancer

Zhu

Spitz

Strom

et al. 2002

Intl Journal of Cancer

View full text Add to dashboard Cite

Cytogenetic aberrations on chromosome 9 have been reported to be one of the most frequent genetic changes in lung tumorigenesis. Although many of these changes have been detected in lung carcinoma specimens, there is growing evidence showing the concordance between chromosomal alterations in primary lung tumors and peripheral blood lymphocytes (PBLs). We investigated whether spontaneous aberrations on chromosome 9 in PBLs are associated with the presence of lung cancer and with a family history of cancer. A personal interview, to construct a detailed epidemiologic profile including family history of cancer, was conducted on 174 lung cancer cases and 162 matched controls. One hundred metaphases from PBLs of each subject were analyzed for chromosome 9 aberrations using the whole chromosome painting technique. Overall, the mean proportion of individuals with chromosome 9 abnormalities in their PBLs was significantly higher in cases (96.0%) than in controls (60.5%) (p < 0.05). After adjustment by age, gender, ethnicity, family size, and pack-years, there was a 16.63-fold significantly elevated odds ratio (OR) for lung cancer associated with chromosome 9 aberrations. When subjects were categorized by frequencies of the chromosome 9 lesions, we observed significantly increased odds ratios of 11.13 (4.66, 26.58) and 27.45 (11.15, 67.54) for individuals with 1 chromosome 9 aberration and >2 chromosome 9 aberrations, respectively. By performing family history analyses, we further observed that control individuals with chromosome 9 aberrations were more likely to report a family history of any cancer (OR ‫؍‬ 1.67 [0.84, 3.32]) and lung cancer (OR ‫؍‬ 2.49 [0.81, 7.67]). Our findings suggest that chromosome 9 aberrations in PBLs might be considered a marker of lung cancer predisposition and may be associated with familial aggregation of cancer.

show abstract

Identification of two distinct tumor-suppressor loci on the long arm of chromosome 10 in small cell lung cancer

Cited by 77 publications

References 20 publications

TSG101 is not mutated in lung cancer but a shortened transcript is frequently expressed in small cell lung cancer

TSG101 is not mutated in lung cancer but a shortened transcript is frequently expressed in small cell lung cancer

Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines

A case‐control analysis of lymphocytic chromosome 9 aberrations in lung cancer

Contact Info

Product

Resources

About