Multiplex mutation screening by mass spectrometry in gastrointestinal stromal tumours.

Abstract:

AIMS:Clinical decision making and optimal clinical trial design based on cancer genetic information will be increasingly informed by the mutational status of multiple genes. METHODS:We performed mutation screening on 22 fresh frozen gastrointestinal stromal tumours (GISTs) using a multiplexed oncogene screening panel with a mass spectroscopy readout (MassARRAY). The panel can detect 390 known mutations across 30 genes, including several known to contribute to intracellular signalling in cancers (BRAF, PIK3CA, KRAS HRAS, NRAS, AKT1, CTNNB1, GNAQ, CDK4, MAP2K1 and MAP2K2). RESULTS:Direct Sanger sequencing confirmed that 16 cases (73%) harboured KIT mutations, affecting exon 11, 13 and 17, and the remaining six were wild-type for both KIT and PDGFRA. The sensitivity of the multiplexed oncogene screening panel was 100% for identifying missense mutations in KIT. Only 17% of the deletion mutations were detected, because the panel was not designed for detecting these. A substitution in FBX4 exon 1 (S8R), representing a germline single-nucleotide polymorphism, was observed in a case with KIT exon 11 missense mutation. No other mutations were identified, including in the six wild-type GISTs. CONCLUSIONS:Our results indicate that mutations other than KIT or PDGFRA are rare in GISTs. Although multiplex mutation screening by mass spectrometry detected missense mutations accurately, it is not sufficient to screen mutations because deletion mutations are common in GISTs.

journal_name

Pathology

journal_title

Pathology

authors

Kang G,Lee J,Jang KT,Beadling C,Corless CL,Heinrich MC,Park JO,Kang WK,Park CK,Kim KM

doi

10.1097/PAT.0b013e3283559c45

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

460-4

issue

5

eissn

0031-3025

issn

1465-3931

journal_volume

44

pub_type

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