Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas

Vasmatzis, George; Johnson, Sarah H.; Knudson, Ryan A.; Ketterling, Rhett P.; Braggio, Esteban; Fonseca, Rafaël; Viswanatha, David S.; Law, Mark E.; Kip, N. Sertac; Özsan, Nazan; Grebe, Stefan K.; Frederick, Lori; Eckloff, Bruce W.; Thompson, E. Aubrey; Kadin, Marshall E.; Milošević, Dragana; Porcher, Julie C.; Asmann, Yan W.; Smith, Jeremy C.; Kovtun, Irina V.; Ansell, Stephen M.; Doğan, Ahmet; Feldman, Andrew L.

doi:10.1182/blood-2012-03-419937

Cited by 206 publications

(207 citation statements)

References 45 publications

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“…Concordant mapping mate pair sequencing reads were used to determine frequency coverage levels across the genome. 31,32 Fluorescence In Situ Hybridization…”

Section: Isolation Of Dna and Mate Pair Sequencingmentioning

confidence: 99%

“…28 Libraries were prepared using the Illumina Mate Pair (MP) Kit following the manufacturer's instructions and sequenced as two libraries per lane on the Illumina HiSeq platform. [27][28][29][30][31] Data were processed using previously described binary indexing mapping algorithms developed in our group. 32 The read-to-reference-genome-mapping algorithm was modified to map both mate pair sequencing reads across the whole genome.…”

Section: Isolation Of Dna and Mate Pair Sequencingmentioning

confidence: 99%

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Integrated analysis of the genomic instability of PTEN in clinically insignificant and significant prostate cancer

et al. 2016

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Patients with clinically insignificant prostate cancer remain a major over-treated population. PTEN loss is one of the most recurrent alterations in prostate cancer associated with an aggressive phenotype, however, the occurrence of PTEN loss in insignificant prostate cancer has not been reported and its role in the separation of insignificant from significant prostate cancer is unclear. An integrated analysis of PTEN loss was, therefore, performed for structural variations, point mutations and protein expression in clinically insignificant (48 cases) and significant (76 cases) prostate cancers treated by radical prostatectomy. Whole-genome mate pair sequencing was performed on tumor cells isolated by laser capture microdissection to characterize PTEN structural alterations. Fluorescence in situ hybridization probes were constructed from the sequencing data to detect the spectrum of these PTEN alterations. PTEN loss by mate pair sequencing and fluorescence in situ hybridization occurred in 2% of insignificant, 13% of large volume Gleason score 6, and 46% of Gleason score 7 and higher cancers. In Gleason score 7 cancers with PTEN loss, PTEN alterations were detected in both Gleason pattern 3 and 4 in 57% of cases by mate pair sequencing, 75% by in situ hybridization and 86% by immunohistochemistry. PTEN loss by sequencing was strongly associated with TMPRSS2-ERG fusion, biochemical recurrence, PTEN loss by in situ hybridization and protein loss by immunohistochemistry. The complex nature of PTEN rearrangements was unveiled by sequencing, detailing the heterogeneous events leading to homozygous loss of PTEN. PTEN point mutation was present in 5% of clinically significant tumors and not in insignificant cancer or high-grade prostatic intraepithelial neoplasia. PTEN loss is infrequent in clinically insignificant prostate cancer, and is associated with higher grade tumors. Detection of PTEN loss in Gleason score 6 cancer in a needle biopsy specimen indicates a higher likelihood of clinically significant prostate cancer. The tumor suppressor gene, PTEN (phosphatase and tensin homolog on chromosome 10), a phosphoinositide 3-phosphatase, negatively regulates the PI3K/ AKT signaling pathway and functions as a tumor suppressor. It is one of the most commonly altered genes in prostate cancer. Mutations in PTEN occur in up to 10% of primary prostate cancers while PTEN deletion occurs in 10-70% of surgically treated cancers and over 50% of metastatic prostate cancers. 1-11 PTEN deletion is associated with poorer cancer specific outcomes, and there is an association of deletion with increasing stage and Gleason score. 7,9,[12][13][14][15][16] Although associated with later stage and higher grade tumors, the frequency of PTEN loss is reported in 3-10% of Gleason score 6 cancers, and 15% of confined pT2 tumors. 12,15 In regards to the proposed precursor lesion, high-grade prostatic intraepithelial neoplasia, the data are inconsistent and limited with five studies to date. In three studies

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“…Concordant mapping mate pair sequencing reads were used to determine frequency coverage levels across the genome. 31,32 Fluorescence In Situ Hybridization…”

Section: Isolation Of Dna and Mate Pair Sequencingmentioning

confidence: 99%

Section: Isolation Of Dna and Mate Pair Sequencingmentioning

confidence: 99%

Integrated analysis of the genomic instability of PTEN in clinically insignificant and significant prostate cancer

et al. 2016

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“…In particular, novel TP63 rearrangements encoding fusion proteins homologous to ΔNp63, a dominant-negative p63 isoform that inhibits the p53 pathway are seen in around 6% of PTCLs and associated with inferior overall survival. Because TP53 mutations are rare in PTCL, these findings suggest that a constellation of alternate genetic abnormalities may contribute to disruption of p53-associated tumour suppressor function in PTCLs [7].…”

Section: Introductionmentioning

confidence: 99%

VIII. New markers in peripheral T‐cell lymphomas: more entities or more confusion?

Gaulard

Leval

2013

Hematological Oncology

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“…DUSP22 rearrangements are associated with decreased expression of the dual-specificity phosphatase gene, DUSP22; lack of cytotoxic marker expression; favorable prognosis; and distinct morphologic features (King, Dao et al 2016). Rearrangements involving TP63, most often partnering with TBL1XR1/ occur in ~8% of ALCL, ALK-negative and have been associated with poor prognosis (Vasmatzis, Johnson et al 2012;Parrilla Castellar, Jaffe et al 2014). …”

Section: Cytogenetics Morphologicalmentioning

confidence: 99%

Anaplastic large cell lymphoma, ALK-negative

Boddicker¹,

Feldman²

2018

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas

Cited by 206 publications

References 45 publications

Integrated analysis of the genomic instability of PTEN in clinically insignificant and significant prostate cancer

Integrated analysis of the genomic instability of PTEN in clinically insignificant and significant prostate cancer

VIII. New markers in peripheral T‐cell lymphomas: more entities or more confusion?

Anaplastic large cell lymphoma, ALK-negative

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