title: Detection of gene copy number aberrations in mantle cell lymphoma by a single quantitative multiplex PCR assay: clinicopathological relevance and prognosis value.
abstract: The t(11;14)(q13;q32) is the hallmark of mantle cell lymphoma (MCL). Additional genetic alterations occur in the majority of cases. This study aimed to design a polymerase chain reaction (PCR) assay to determine the incidence and relevance of recurrent gene copy number aberrations in this disease. Forty-two MCL cases with frozen- or paraffin-embedded (FFPE) tissues were selected. Three different quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF) assays were designed to simultaneously analyse eight genes (CDKN2A, RB1, ATM, CDK2, TP53, MYC, CDKN1B, MDM2), to analyse the 9p21 locus (CDKN2A/CDKN2B) and FFPE tissues. Gains of MYC, CDK2, CDKN1B, and MDM2 were observed in 10% of cases. Losses of RB1, CDKN2A, ATM or TP53 were observed in 38%, 31%, 24% and 10% of cases, respectively. Analysis of the 9p21 locus indicated that, in most cases, tumours displayed a complete inactivation of p14(ARF)/p15I(NK4B)/p16I(NK4A). CDKN2A and MYC aberrations were associated with a high MCL international prognostic index (MIPI). CDK2/MDM2 gains and CDKN2A/TP53 losses correlated with an unfavourable outcome. PCR experiments with frozen and FFPE-tissues indicated that our approach is valid in a routine diagnostic setting, providing a powerful tool that could be used for patient stratification in combination with MIPI in future clinical trials.
authors: Inserm U918, Centre Henri Becquerel and European Institute of Peptide Research (IFR23), Rouen, France. fabrice.jardin@rouen.fnclcc.fr
authors: Fabrice
authors: F
authors: Jardin
authors: Jean-Michel
authors: JM
authors: Picquenot
authors: Françoise
authors: F
authors: Parmentier
authors: Philippe
authors: P
authors: Ruminy
authors: Marie
authors: M
authors: Cornic
authors: Dominique
authors: D
authors: Penther
authors: Philippe
authors: P
authors: Bertrand
authors: Hélène
authors: H
authors: Lanic
authors: Ophélie
authors: O
authors: Cassuto
authors: Catherine
authors: C
authors: Humbrecht
authors: Emilie
authors: E
authors: Lemasle
authors: Agathe
authors: A
authors: Wautier
authors: Christian
authors: C
authors: Bastard
authors: Hervé
authors: H
authors: Tilly
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D015994:Incidence; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D015203:Reproducibility of Results; D016019:Survival Analysis