HHE Pathology and diagnostics supplement 2018 - Page 14

pathology and diagnostics The new kid on the block Next generation sequencing is practical and reliable to use on tissue specimens and potentially on liquid biopsies, which potentially will further revolutionise the diagnostic landscape of lung cancer Marvin Lim Chang Jui MBBCh BAO BA MRCPUK Anne-Marie Baird BSc (Hons) PG Dip (Statistics) PhD Stephen Finn MB BAO BCh FDS PhD FRCPath FFPATH Trinity College Dublin, School of Medicine, Dublin, Ireland Lung cancer continues to be the major cause of cancer-related death globally. 1 More than two-thirds of lung cancer patients present with advanced disease, 2,3 which excludes the option of potentially curative treatments. Another important reason accounting for the high mortality rate is excessive mutational load in patients with smoking history, a phenomenon central to the pathogenesis of lung cancer progression, compared with patients with age-related cancers. 4 Five-year survival of all patients with lung cancer is only 18%. 5 Recently, great advances have been made in terms of screening, minimally invasive techniques for diagnosis and new treatments. 6–9 The recognition of genetic driver mutations in NSCLC has paved the way for the development of targeted therapies, which often provides outstanding responses in patients harbouring specific genetic mutations. 10,11 Approximately two thirds of lung adenocarcinomas contain actionable driver mutations, which can be detected using comprehensive molecular profiling. 11–13 ALK gene rearrangement in NSCLC was first discovered by Japanese researchers a decade ago. 14 This gene rearrangement, which precipitates expression of oncogenic fusion proteins, is found in approximately 3–7% of patients with metastatic lung carcinoma based on early studies using reverse transcription- polymerase chain reaction (RT-PCR) and fluorescence in situ hybridisation (FISH). 14,15 ALK gene fusion with echinoderm microtubule- associated protein like 4 (EML 4) represents the most frequent rearrangement among the ALK alterations. 12,16 Other fusion partners have also been \ܝYX\•T KSH MHB[ PLK M$̌\\Y][\][[HX][[\\HZYH[][ۈ܈\]Y\\H\H\ [[HX]Y[܈S\]]Bˈ HXۙ Y[\][ۈS[X]ܜX\\][X[[X[X]HۛHY[ۈHYX]H[H\ [[HX]Y[][]\H[YX]H[]Y[™][ܚ^[X\\[K $̍[ LHܘ[YH\ݘ[وܚ^[X܂X]Y[وY]\]XS\]]H]T\\[[ۈXYۛX\YۈYXXH[Y]H]Hو\HRH[RRBYY\ˈ K B[X\X\]YBT\\[HH[X\X\]YH܂XYۛ\وSX\[[Y[]\Y]X[\\\][ۈ[[[[\]][ۂXܙ[ZY[[\\X\\H܈XY][˜X\]H\[ˈ\]\^[]KX\B[[]H[\]Z\\HY][و]B^\\K $̎Hۈ\H\[ۜTX^BXH\]Z][\[X]\H[ x$L HقH]HوX\[[Y[و]]H[™[][H[Hو L8$̌ N]\B\[X\Y] [ٙ܈]]H[\ MIH܂[ܙK H[[][\[Z\H RH\[\Y]][H\Y܈SXYۛ\[[˜[\[R\[[ۈXYۛX\^H\˜\ݙY[ MH\Yۈ]X[]HX\][BY[YH]Y[]S\X\[Yˈ ̋ [YR\Y[^[][H\Y[Xܘ]ܚY\YHHYX][\]š[\]][ۈ\]Z\\^\Y[H[\[BZ[^\[ۈX^HHX[[\\]]\X[SœX\[[Y[ B\]H\B[Z]][ۜSRš\Z[[[[BHXۚ][ۈو[]Xš[]\H\B]\]]][ۜ[\‘Y\ݙ\B[X\H\\X[BH\ݙ\HوSœ]YH^H܈H][Y[[H\\\XX\[[Y[Y]TZ[›و\]Y\\Y\˜Y[وܚ^[X\ܛYYۛH˜H\[H[\Bۙ\H]]H܂[X]܈ JH]\[X]]HYZ[S˂\]Z][R\[ˈ ͸$]\H]YY\]H\ܝY[HY]]H\[ܚ^[XYH\ۜH]Hو H]\[RX[X[H\^Y[œܙ\[ۋYYH\][ Hو L H[۝œ]Y[HXZ][[\و\B\\Y]H\ۜH]Hو IH]X]Y[ K H[X[\XYۛ\[\\›و [۝[[\][[HX]H[Z]][ۜوT[RZ]\\B[[\\H Z]\\][܈\][[[ۙH\^H܈[ۘ\]Z]\T\[Y]^Y K H\\\[܈]YBMH N][X[\K