Prediction of response to anti-EGFR antibody-based therapies by multigene sequencing in colorectal cancer patients.

LUPINI, Laura, Cristian BASSI, Jitka MLČOCHOVÁ, Gentian MUSA, Marta RUSSO, Petra VYCHYTILOVÁ, Marek SVOBODA, Silvia SABBIONI, Radim NĚMEČEK, Ondřej SLABÝ a Massimo NEGRINI. Prediction of response to anti-EGFR antibody-based therapies by multigene sequencing in colorectal cancer patients. BMC Cancer. LONDON: BIOMED CENTRAL LTD, 2015, roč. 15, October, s. nestránkováno, 11 s. ISSN 1471-2407. Dostupné z: https://dx.doi.org/10.1186/s12885-015-1752-5.

Základní údaje

• Originální název: Prediction of response to anti-EGFR antibody-based therapies by multigene sequencing in colorectal cancer patients.
• Autoři: LUPINI, Laura (380 Itálie), Cristian BASSI (380 Itálie), Jitka MLČOCHOVÁ (203 Česká republika, domácí), Gentian MUSA (380 Itálie), Marta RUSSO (380 Itálie), Petra VYCHYTILOVÁ (203 Česká republika, domácí), Marek SVOBODA (203 Česká republika, domácí), Silvia SABBIONI (380 Itálie), Radim NĚMEČEK (203 Česká republika), Ondřej SLABÝ (203 Česká republika, garant, domácí) a Massimo NEGRINI (380 Itálie).
• Vydání: BMC Cancer, LONDON, BIOMED CENTRAL LTD, 2015, 1471-2407.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 30200 3.2 Clinical medicine
• Stát vydavatele: Velká Británie a Severní Irsko
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 3.265
• Kód RIV: RIV/00216224:14740/15:00084505
• Organizační jednotka: Středoevropský technologický institut
• Doi: http://dx.doi.org/10.1186/s12885-015-1752-5
• UT WoS: 000363502400001
• Klíčová slova česky: kolorektální karcinom; resistence k anti-EGFR protilátkám; mutace genů; sekvenování nové generace
• Klíčová slova anglicky: colorectal cancer; resistance to anti-EGFR antibodies; gene mutations; next-generation sequencing
• Štítky: rivok
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

Background: The anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (moAbs) cetuximab or panitumumab are administered to colorectal cancer (CRC) patients who harbor wild-type RAS proto-oncogenes. However, a percentage of patients do not respond to this treatment. In addition to mutations in the RAS genes,mutations in other genes, such as BRAF, PI3KCA,or PTEN, could be involved in the resistance to anti-EGFR moAb therapy. Methods: In order to develop a comprehensive approach for the detection of mutations and to eventually identify other genes responsible for resistance to anti-EGFR moAbs, we investigated a panel of 21 genes by parallel sequencing on the Ion Torrent Personal Genome Machine platform. We sequenced 65 CRCs that were treated with cetuximab or panitumumab. Among these, 37 samples were responsive and 28 were resistant. Results: We confirmed that mutations in EGFR-pathway genes (KRAS, NRAS , BRAF, PI3KCA) were relevant for conferring resistance to therapy and could predict response (p = 0.001). After exclusion of KRAS, NRAS, BRAF and PI3KCA combined mutations could still significantly associate to resistant phenotype ( p = 0.045, by Fisher exact test). In addition, mutations in FBXW7 and SMAD4 were prevalent in cases that were non-responsive to anti-EGFR moAb. After we combined the mutations of all genes (excluding KRAS), the ability to predict response to therapy improved significantly (p = 0.002, by Fisher exact test). Conclusions: The combination of mutations at KRAS and at the five gene panel demonstrates the usefulness and feasibility of multigene sequencing to assess response to anti-EGFR moAbs. The application of parallel sequencing technology in clinical practice, in addition to its innate ability to simultaneously examine the genetic status of several cancer genes, proved to be more accurate and sensitive than the presently in use traditional approaches.

Návaznosti

• ED1.1.00/02.0068, projekt VaV: Název: CEITEC - central european institute of technology