Table 7.
Systematic Review of Genetic Alterations at the PTEN and CDKN2A Loci in Chordomas
| No. | Author (Year) | Materials/Objects | Method | Findings |
|---|---|---|---|---|
| 1 | Mertens et al (1994)11 | Human sacral chordoma samples (n=3) | Chromosome banding analysis | Karyotype included del(9) and –10 in one case. |
| 2 | Scheil et al (2001)4 | Human chordoma samples (n=16); U-CH1 cell line | Comparative genomic hybridization; chromosome banding analysis; FISH | Loss of 9p was identified in 5 of 16 (31%) cases, and loss of chromosome 10 segment was noted in 3 of 16 (19%) cases; U-CH1 had del(9) and del(10) chromosomal abnormalities. |
| 3 | Kuźniacka et al (2004)5 | Human chordoma samples (n=7) | Chromosome banding analysis | Loss of chromosome 10 segment was noted in 3 of 7 (43%) cases, and loss of 9p sequences was identified in 2 of 7 (29%) cases. |
| 4 | Hallor et al (2008) | Human chordoma samples (n=26) | Array comparative genomic hybridization; FISH | Heterozygous deletion at 9p21 covering the CDKN2A locus was observed in 15 of 26 (58%) tumor samples, homozygous deletion was found in 3 of 26 (12%) samples. |
| 5 | Han et al (2009)34 | Human chordoma samples (n=11), and U-CH1 cell line | Immunohistochemistry; western-blotting | Weak PTEN staining was demonstrated in 4 of 11 (36%) cases, and 6 of 11 (55%) cases were negative for PTEN staining, whereas 1 (9%) case showed positive PTEN staining; PTEN expression was not observed in U-CH1 cells. |
| 6 | Presneau et al (2009)35 | Human chordoma samples (n=50) | Immunohistochemistry | PTEN displayed no immunoreactivity in 7 of 43 (16%) chordoma samples, and CDKN2A showed no immunoreactivity in 46 of 48 (96%) chordoma samples. |
| 7 | Sommer et al (2010)36 | Human chordoma samples (n=27) | Immunohistochemistry | CDKN2A expression was absent in 20 of 27 (74%) chordomas. There was no significant difference in median disease-free survival between CDKN2A-positive chordomas (90 months) and negative chordomas (24 months). |
| 8 | Horbinski et al (2010)13 | Human clival chordoma samples (n=28) | FISH; PCR-based microsatellite LOH analysis | 9p LOH was identified in 3 of 25 (12%) samples, and 10q LOH was found in 12 of 21 (57%) samples; FISH identified homozygous loss of the 9p21 locus in 5 of 23 (22%) cases. |
| 9 | Brüderlein et al (2010)7 | U-CH1 and U-CH2 chordoma cell lines | Array comparative genomic hybridization | Both U-CH1 and U-CH2 showed biallelic loss of the CDKN2A locus on chromosome 9p21; loss of the PTEN locus was noted in U-CH1, but not in U-CH2. |
| 10 | Shalaby et al (2010)37 | Human chordoma samples (n=147) | Immunohistochemistry | PTEN expression was absent in 19 of 147 (13%) analyzed chordomas. |
| 11 | Le et al (2011)6 | Human chordoma samples (n=20) | Array comparative genomic hybridization | Loss of CDKN2A was observed in 16/20 (80%) cases, six of which showed homozygous deletion; loss of PTEN was found in 16/20 (80%) cases; no mutations were found in any of the 21 chordoma samples. |
| 12 | Dewaele et al (2011)14 | Human chordoma samples (n=42) | FISH | Loss of PTEN was observed in 7 of 18 (39%) analyzed samples. |
| 13 | Rinner et al (2012)9 | MUG-Chor1 chordoma cell line | Affymetrix GeneChip Human Mapping SNP 6.0 array | The cell line displayed chromosomal loss at 10p15.3-q23.32 (includes the PTEN locus), and a homozygous loss was seen at 9p24.3-p13.1 (includes the CDKN2A locus). |
| 14 | Diaz et al (2012)17 | Human chordoma samples (n=22) | Genome-wide high-resolution SNP-array | Loss of 9p involving CDKN2A was identified in 4 of 18 (22%) chordoma samples. |
| 15 | Choy et al (2014)8 | Human chordoma samples (n=45) | Matrix-assisted laser desorption/ionization time-of-flight mass spectrometer | A nonsense mutation (p.R130*) in PTEN was identified in 1 of 45 (2.2%) chordoma samples; a nonsense mutation (p.R58*) was identified in CDKN2A in 2 of 45 (4.4%) chordoma samples. |
| 16 | Chen et al (2014)38 | Human sacral chordoma samples (n=40) | Immunohistochemistry | Positive expression of PTEN was observed in 10/40 (25%) chordoma samples; patients with negative PTEN expression had a poorer prognosis than those with positive PTEN expression (P=0.011). |
| 17 | Lee et al (2015)16 | Human chordoma samples (n=23) | PCR-based microsatellite LOH analysis | LOH was observed at 10q23 (includes the PTEN locus) in 6 of 23 (26%) specimens; chordoma tissues with LOH at 10q23 showed decreased or absent PTEN expression, and those without LOH at 10q23 demonstrated positive PTEN expression. |
| 18 | Wang et al (2016)18 | Human chordoma samples (n=24) | Genome-wide high-resolution SNP-array | Copy number loss of CDKN2A was identified in 12 of 22 (55%) chordoma samples, and homozygous deletion of CDKN2A was detected in 5 of 22 (23%) samples. |
| 19 | Cottone et al (2020)15 | Human chordoma samples (n=384) | Immunohistochemistry; FISH | Complete loss of chromosome 9 was observed in 3 cases; Positive CDKN2A protein expression was noted in 141 of 303 (47%) samples; copy number loss of CDKN2A gene was found in 138 of 274 (50%) samples, including heterozygous loss in 44 samples and homozygous loss in 48 samples. |
Abbreviations: FISH, fluorescent in situ hybridization; LOH, loss of heterozygosity.