Loss of heterozygosity in human germinal tumors

Radice, P.; Lacerenza, S.; Mondini, P; Radice, Maria Teresa; Pilotti, Silvana; Porta, Giuseppe Della

doi:10.1159/000132843

Cited by 30 publications

(23 citation statements)

References 4 publications

(4 reference statements)

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“…Abnormalities of chromosome Sq have been studied in other cancers at the cytogenetic level (31)(32)(33)(34) and by Southern blotting (35)(36)(37)(38)(39)(40)(41)(42)(43). In some tumors, such as ovarian and germinal cancers, no LOH was detected (35,36); in others, LOH was detected in 9-60% (37-41).…”

Section: Discussionmentioning

confidence: 99%

Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers.

Boynton

Blount

Yin

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

186

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The tumor suppressor gene APC was recently identified, and the cDNA was cloned from chromosome 5q21. Point mutations affecting APC are seen in the hereditary syndrome familial adenomatous polyposis, and point mutations in APC and a closely linked gene, MCC, as well as loss of heterozygosity involving chromosome 5q have been reported in sporadic colon cancer. To our knowledge, loss of heterozygosity involving APC or MCC or both has not yet been described in any other human cancer besides lung cancer. We used the polymerase chain reaction and DNA content flow cytometric nuclear sorting to examine 30 primary human esophageal cancers for loss of heterozygosity ofAPC or MCC or both. Loss of one allele was detected in 77% of 26 informative cases. These data suggest that loss of heterozygosity of regions on Sq including the APC and MCC genetic loci is involved in the development and/or progression of most human esophageal cancers.

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Section: Discussionmentioning

confidence: 99%

Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers.

Boynton

Blount

Yin

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

186

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“…In human testicular cancer these putative processes are poorly understood. Involvement of tumour suppressor genes that act in a recessive manner is suggested by loss of heterozygosity in some areas of the genome in tumour DNA (Lothe et al, 1989;Radice et al, 1989;Rukstalis et al, 1989;Peltomaki et al, 1990). As cellular oncogenes are thought to participate in the regulation of cell differentiation -which is a prominent feature of testesalterations of oncogenes are of obvious interest in testicular tumours of germ cell origin.…”

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confidence: 99%

Oncogenes in human testicular cancer: DNA and RNA studies

Peltomäki

Alfthan²,

Chapelle³

1991

Br J Cancer

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Oncogene dosage and expression were studied in 16 testicular neoplasms, 14 of germ cell and two of non-germ cell origin. In comparison with normal DNA, tumour DNA of a total of eight patients (seven with germ cell neoplasm and one with testicular lymphoma) showed increased dosages of KRAS2, PDGFA, EGFR, MET and PDGFB. The most frequent (occurring in six tumours) and prominent (up to 3-4-fold) increases were detected in the dosages of KRAS2 (on chromosome 12p) and PDGFA (chromosome 7p), relative to a reference locus from chromosome 2. Importantly, there was a similar increase in 12p dosage in general in these tumours, suggesting the presence of the characteristic isochromosome 12p marker. On the contrary, possible 7p polysomy (assessed by molecular methods) did not explain the PDGFA (or EGFR) changes in all cases. NRAS, MYCN, CSFIR, MYB, MYC, ABL, HRASI, TP53, and ERBB2 did not reveal any consistent alterations in tumour DNA. In RNA dot blot assays the expression of KRAS2, PDGFA, EGFR, or MYC was generally not increased in the tumour samples when compared to that in normal testicular tissue of the same patients although there was interindividual variation in mRNA levels. It thus appears that while oncogene dosage changes occur in a proportion of testis cancers, they are often part of changes in large chromosomal regions or whole arms and are seldom accompanied by altered expression. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6

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“…This and the frequency of LOH (57%), which is comparable to the one in Wilms tumor on band llpl3 (41), strongly suggest the presence of a tumor-suppressor gene within this region. Radice et aL (38) have described LOH in 4 of 12 testicular cancers (Fig. 4).…”

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confidence: 94%

“…Thus it remains unclear whether this LOH region includes the entire telomere. The same region has also been implicated in the pathogenesis of breast cancer (31), rhabdomyosarcoma (15), Wilms tumor (35,36), bladder cancer (37), and testicular cancer (38). These data are schematically summarized in Fig. …”

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confidence: 99%

“…The recent description of loss of genetic imprinting for IGF2 in Wilms tumor (42,43), however, suggests that loss of genetic control elements adjacent to the IGF2/HI9 genes could be the important event within this Wilms tumor LOH domain. There also appears to be some overlap of the second NSCLC region regions (31)(32)(33)(34); U, rhabdomyosarcoma regions (15,30); C, Wilms tumor 2 regions (35,36); A, bladder cancer region (37); Es, testicular cancer region (38).…”

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Three tumor-suppressor regions on chromosome 11p identified by high- resolution deletion mapping in human non-small-cell lung cancer

1995

Lung Cancer

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Non-small-cell lung cancer is the leading cause of cancer death for men and women in the ind ald nations. Identification of regions for genes involved in its pathogenesis has been difficult. Data presented here show three distinct regions identified on chromosome 11p. Two regions on 11pl3 distal to the Wilms tumor gene WT1 and on 11pl1.5 between the markers HBB and DIIS860 are described. The third region on the telomere of 11plS.5 has been previously described and is further delineated in this communication. By high-resolution mapping the size of each of these regions was estimated to be 2-3 megabases. The frequency of somatic loss of genetic information in these regions (57%, 71%, and 45%, respectively) was comparable to that seen in heritable tumors such as Wilms tumor (55%) and retinoblastoma (70%) and suggests their involvement in pathogenesis of non-small-cell lung cancer. Gene dosage analyses revealed duplication of the remaining allele in the majority of cases in the 11pl3 and the proximal 11p15.5 region but rarely in the distal 11pl5.5 region. In tumors with loss of heterozygosity in all three regions any combination of duplctin or simple deletion was observed, suggesting that loss ofheterozygosity occurs independently and perhaps at different points in time. These results provide a basis for studies directed at cloning potential tumor-suppressor genes in these regions and for assessing their biological and clinical sgnifcance In non-small-cell lung cancer.Non-small-cell lung cancer (NSCLC) comprises all primary malignant lung tumors except small-cell tumors and accounts for 80%o of all lung cancers. Many reasons should place NSCLC in the front line ofcancer research. Some ofthese are as follows: (i) the annual incidence of lung cancer is --3 x 106 worldwide and continues to rise; (ii) the number of young individuals without exposure to tobacco, in particular women, is rising; (iii) 87% of patients with NSCLC will die of the disease, and approximately 115,000 people annually succumb to NSCLC in the United States; (iv) the 5-year survival rate of 13% has not changed appreciably in the last 20 years; (v) screening of high-risk individuals with frequent chest radiographs and sputum cytological examinations was proven unsuccessful; and (vi) fresh specimens and wellcharacterized immortalized cell lines are now available (1). The molecular genetic data presented here will provide a focus for investigations to isolate genetic elements involved in NSCLC development and progression.The identification of regions for genes involved in the pathogenesis of NSCLC has been difficult because a possible familial rsk is obscured by environmental risk factors (2, 3) and because cytogenetic analyses have shown complex aberrations (4, 5). Molecular genetic studies have implicated chromosomes 3 (6, 7), 5 (8), 8 (9), 9 (10, 11), 11 (12, 13), and 17 (12) as possibly carrying disease-related regions. The present study was performed to specifically address whether chromosome 11 harbors NSCLC regions.Mechanisms by which re...

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Loss of heterozygosity in human germinal tumors

Cited by 30 publications

References 4 publications

Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers.

Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers.

Oncogenes in human testicular cancer: DNA and RNA studies

Three tumor-suppressor regions on chromosome 11p identified by high- resolution deletion mapping in human non-small-cell lung cancer

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