Lung: Translocations in Squamous Cell Carcinoma

2014-10-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note: the fusion was discovered by NGS. Many chromosome rearrangement mechanisms such as translocation, inversion,deletion or complex rearrangement may lead to the same fusion)

Classification

Classification

In the group of malignant epithelial tumours of the lungs, squamous cell carcinomas belong to the non-small cell carcinomas (non-small cell lung cancer (NSCLC)), as opposed to small cell carcinomas (SCLC). Other NSCLCs are: adenocarcinomas, adenosquamous carcinomas, large cell carcinomas, sarcomatoid carcinomas, carcinoid tumours, salivary gland tumours.

Clinics and Pathology

Epidemiology

Squamous cell carcinoma is the most frequent lung cancer in male patients, representing about 40% of the cases, and only 25% in women (much less frequent in female patients than adenocarcinoma). Squamous cell carcinoma is the lung cancer the most often associated with tobacco smoking. Location of the tumour is usually central, present as a perihilar mass, with or without lobar collapse and obstructive pneumonitis, but it can also be peripheral at times.

Pathology

There are small cell variants (differential diagnosis: SCLC), clear cell variants, well-differentiated papillary variants, basaloid variants with a very aggressive clinical course, and spindle cell (sarcomatoid) carcinosarcoma variants of the typical squamous cell carcinoma.
The expression of cytokeratins (CK) CK5/6, CK34BE12 and TP63 (3q28, also called P63) are strong in squamous cell carcinoma, whereas the expression of CK7 and NKX2-1 (14q13, also called TTF-1) are strong in adenocarcinoma (Xu et al., 2014).

Evolution

Staging is performed according to the TNM system.

Genetics

Note

TP53 (17p13) mutations are detected in most cases. In a large recent study, altered pathways included NFE2L2/KEAP1 in 34%, squamous differentiation genes in 44%, PI3K/AKT in 47%, and CDKN2A/RB1 in 72% of tumors. In contrast to what is found in adenocarcinoma, mutations in EGFR (7p11) or in KRAS (12p12) are extremely rare in squamous cell carcinoma of the lungs (Cancer Genome Atlas Research Network, 2012). DDR2 (1q23) is inactivated in about 4% of cases; FGFR1 (8p11) and FGFR3 (4p16) are amplified in 5 to 10% of cases (Majewski et al., 2013; Seo et al., 2014).

Cytogenetics

Cytogenetics morphological

The translocations are the following:
t(1;1)(p36;p36) PRKCZ/SKI (Majewski et al., 2013)
t(1;1)(p34;q44) SMYD3/ELOVL1 (Cancer Genome Atlas Research Network, 2012)
t(1;1)(q21;q21) GATAD2B/PRKAB2 (Cancer Genome Atlas Research Network, 2012)
t(1;2)(p35;q37) ZBTB8B/TRAF3IP1 (Cancer Genome Atlas Research Network, 2012)
t(1;2)(p12;p16) REL/MAN1A2 (Cancer Genome Atlas Research Network, 2012)
t(1;2)(p12;p15) PHGDH/WDPCP (Cancer Genome Atlas Research Network, 2012)
t(1;3)(p34;q26) ATP11B/POU3F1 (Cancer Genome Atlas Research Network, 2012)
t(1;3)(p34;q26) OSCP1/SOX2-OT (Cancer Genome Atlas Research Network, 2012)
t(1;3)(p33;q29) TFRC/NSUN4 (Cancer Genome Atlas Research Network, 2012)
t(1;4)(p31;q22) BMPR1B/ALG6 (Cancer Genome Atlas Research Network, 2012)
t(1;5)(p34;q31) CTNNA1/HEYL (Cancer Genome Atlas Research Network, 2012)
t(1;5)(q25;p13) DARS2/ZFR (Cancer Genome Atlas Research Network, 2012)
t(1;8)(p36;q21) SLC7A13/WDTC1 (Cancer Genome Atlas Research Network, 2012)
t(1;8)(p32;q24) NRD1/KCNK9 (Cancer Genome Atlas Research Network, 2012)
t(1;9)(p33;p13) KIF24/FAAH (Cancer Genome Atlas Research Network, 2012)
t(1;10)(p32;q21) CDK1/USP24 (Cancer Genome Atlas Research Network, 2012)
t(1;10)(p31;p14) SFMBT2/PRKACB (Cancer Genome Atlas Research Network, 2012)
t(1;10)(q32;q22) TMEM206/PSAP (Cancer Genome Atlas Research Network, 2012)
t(1;11)(p31;q24) ETS1/NEGR1 (Cancer Genome Atlas Research Network, 2012)
t(1;12)(q25;p12) HMCN1/ETNK1 (Cancer Genome Atlas Research Network, 2012)
t(1;16)(q21;p12) CCP110/GOLPH3L (Cancer Genome Atlas Research Network, 2012)
t(1;17)(p21;q25) UNK/DPYD (Cancer Genome Atlas Research Network, 2012)
t(1;17)(p12;q11) ALDOC/MAN1A2 (Cancer Genome Atlas Research Network, 2012)
t(1;21)(p35;q22) ITSN1/MATN1 (Cancer Genome Atlas Research Network, 2012)
t(2;2)(p25;p25) ROCK2/SH3YL1 (Cancer Genome Atlas Research Network, 2012)
t(2;2)(p24;p23) GPN1/KLHL29 (Cancer Genome Atlas Research Network, 2012)
inv(2)(p21p23) or del(2)(p21p23) EML4/ALK (Rikova et al., 2007; Soda et al., 2007; Martelli et al., 2009)
t(2;2)(p21;p21) THADA/EML4 (Cancer Genome Atlas Research Network, 2012)
t(2;2)(p16;p23) PSME4/PPP1CB (Cancer Genome Atlas Research Network, 2012)
t(2;2)(p15;p15) EHBP1/FAM161A (Cancer Genome Atlas Research Network, 2012)
t(2;2)(q21;q21) GPR39/MGAT5 (Cancer Genome Atlas Research Network, 2012)
t(2;2)(q21;q24) ACVR1C/MGAT5 (Cancer Genome Atlas Research Network, 2012)
t(2;2)(q23;q35) TNS1/RPRM (Cancer Genome Atlas Research Network, 2012)
t(2;3)(p16;q26) KCNMB2/NRXN1 (Cancer Genome Atlas Research Network, 2012)
t(2;4)(p16;q13) BCL11A/EPHA5 (Cancer Genome Atlas Research Network, 2012)
t(2;5)(p16;p15) NRXN1/PLEKHG4B (Cancer Genome Atlas Research Network, 2012)
t(2;5)(p11;p12) HCN1/FUNDC2P2 (Cancer Genome Atlas Research Network, 2012)
t(2;5)(q35;p13) USP37/OSMR (Cancer Genome Atlas Research Network, 2012)
t(2;6)(p24;p22) ID4/FAM84A (Cancer Genome Atlas Research Network, 2012)
t(2;16)(q24;q11) ANKRD26P1/SLC4A10 (Cancer Genome Atlas Research Network, 2012)
t(2;17)(p25;q21) CRHR1-IT1/ALLC (Cancer Genome Atlas Research Network, 2012)
t(2;18)(p24;q11) KLHL29/PSMA8 (Cancer Genome Atlas Research Network, 2012)
t(2;22)(p12;q12) EVA1A/TTC28 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(p12;q29) PAK2/VGLL3 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q11;q13) ALCAM/EPHA6 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q12;q13) GSK3B/IMPG2 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q13;q22) SLCO2A1/GUCA1C (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q21;q22) RUVBL1/TMCC1 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q22;q22) PIK3CB/BFSP2 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q22;q22) TMCC1/C3orf36 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q24;q26) HLTF/OTOL1 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q25;q25) GMPS/C3orf55 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q25;q26) IQCJ/BCHE (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q25;q27) PPM1L/MCF2L2 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q25;q28) PYDC2/C3orf79 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q26;q26) ATP11B/SI (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q26;q26) PHC3/FNDC3B (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q26;q27) CCDC39/MCF2L2 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q26;q28) SOX2/TPRG1 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q27;q28) LPP/ST6GAL1 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q27;q29) EHHADH/SENP5 (Cancer Genome Atlas Research Network, 2012)
t(3;3)(q29;q29) LRCH3/MIR570 (Cancer Genome Atlas Research Network, 2012)
t(3;4)(q26;p16) ATP11B/ZNF595 (Cancer Genome Atlas Research Network, 2012)
t(3;8)(q27;q22) MCF2L2/MIR548A3 (Cancer Genome Atlas Research Network, 2012)
t(3;8)(q29;p12) FYTTD1/WRN (Cancer Genome Atlas Research Network, 2012)
t(3;11)(q26;p15) PDE3B/ATP11B (Cancer Genome Atlas Research Network, 2012)
t(3;13)(q21;q33) TNFSF13B/MYLK (Cancer Genome Atlas Research Network, 2012)
t(3;17)(q25;p11) MAP2K3/SSR3 (Cancer Genome Atlas Research Network, 2012)
t(3;17)(q29;q23) MIR21/WDR53 (Cancer Genome Atlas Research Network, 2012)
t(3;19)(q27;q13) ACTN4/IGF2BP2 (Cancer Genome Atlas Research Network, 2012)
t(3;20)(q21;q13) SLC12A8/BCAS1 (Cancer Genome Atlas Research Network, 2012)
t(3;21)(p11;q21) POU1F1/TMPRSS15 (Cancer Genome Atlas Research Network, 2012)
t(3;22)(q26;q11) ATP11B/TPTEP1 (Cancer Genome Atlas Research Network, 2012)
del(4)(p16p16) FGFR3/TACC3 (Majewski et al., 2013; Wu et al. 2013)
t(4;4)(q13;q22) CCSER1/UGT2A1 (Cancer Genome Atlas Research Network, 2012)
t(4;6)(p15;q22) SLC34A2/ROS1 (Davies et al., 2012)
t(4;8)(q13;q24) COX18/ZFAT (Cancer Genome Atlas Research Network, 2012)
t(4;9)(q13;q32) ADAMTS3/SNX30 (Cancer Genome Atlas Research Network, 2012)
t(4;10)(p13;q11) SGMS1/KCTD8 (Cancer Genome Atlas Research Network, 2012)
t(5;5)(p15;p15) MARCH6/IRX4 (Cancer Genome Atlas Research Network, 2012)
t(5;5)(p15;p15) ROPN1L/SEMA5A (Cancer Genome Atlas Research Network, 2012)
t(5;5)(p12;p13) RICTOR/FGF10 (Cancer Genome Atlas Research Network, 2012)
t(5;6)(q33;q22) CD74/ROS1 (Davies et al., 2012)
t(5;8)(p15;q21) MRPS28/ADAMTS16 (Cancer Genome Atlas Research Network, 2012)
t(5;8)(p13;p11) EIF4EBP1/PRKAA1 (Cancer Genome Atlas Research Network, 2012)
t(5;11)(q14;q22) FAM151B/CASP12 (Cancer Genome Atlas Research Network, 2012)
t(5;11)(q35;q14) KCNIP1/KCTD14 (Cancer Genome Atlas Research Network, 2012)
t(5;12)(p12;q13) NNT/AMIGO2 (Cancer Genome Atlas Research Network, 2012)
t(6;6)(p25;p25) FAM50B/PPP1R3G (Cancer Genome Atlas Research Network, 2012)
t(6;6)(p22;q12) EYS/DEK (Cancer Genome Atlas Research Network, 2012)
t(6;6)(p21;p21) HLA-DOA/MUC21 (Cancer Genome Atlas Research Network, 2012)
t(6;6)(p12;p22) BEND6/TRIM38 (Cancer Genome Atlas Research Network, 2012)
t(6;6)(p12;q14) FAM83B/HTR1E (Cancer Genome Atlas Research Network, 2012)
t(6;6)(q14;q15) GABRR2/ME1 (Cancer Genome Atlas Research Network, 2012)
t(6;13)(p21;q12) RPL7L1/CDK8 (Cancer Genome Atlas Research Network, 2012)
t(6;14)(q24;q24) SASH1/DPF3 (Cancer Genome Atlas Research Network, 2012)
t(6;16)(q13;p13) NTAN1/SLC17A5 (Cancer Genome Atlas Research Network, 2012)
t(7;7)(p11;p12) VOPP1/GRB10 (Cancer Genome Atlas Research Network, 2012)
t(7;7)(q22;q31) ANKRD7/DUS4L (Cancer Genome Atlas Research Network, 2012)
t(7;7)(q31;q33) CHCHD3/MET (Cancer Genome Atlas Research Network, 2012)
t(7;8)(p14;p23) AMPH/FDFT1 (Majewski et al., 2013)
t(7;10)(q36;q25) ACTR3C/SORCS1 (Cancer Genome Atlas Research Network, 2012)
t(8;8)(p11;p11) ADAM9/RNF170 (Cancer Genome Atlas Research Network, 2012)
t(8;8)(p11;p11) BAG4/FGFR1 (Wu et al., 2013)
t(8;8)(p11;p11) LETM2/KCNU1 (Cancer Genome Atlas Research Network, 2012)
t(8;8)(q11;q11) PRKDC/C8orf22 (Cancer Genome Atlas Research Network, 2012)
t(8;8)(q23;q23) CSMD3/ANGPT1 (Cancer Genome Atlas Research Network, 2012)
t(8;8)(q23;q23) OXR1/RSPO2 (Cancer Genome Atlas Research Network, 2012)
t(8;9)(p12;p13) PURG/UBAP1 (Cancer Genome Atlas Research Network, 2012)
t(8;9)(p11;p21) EIF4EBP1/C9orf53 (Cancer Genome Atlas Research Network, 2012)
t(8;10)(p21;q26) FGFR2/KIAA1967 (Wu et al., 2013)
t(8;10)(q23;q11) ANGPT1/CXCL12 (Cancer Genome Atlas Research Network, 2012)
t(8;11)(q21;p15) HTATIP2/CA1 (Cancer Genome Atlas Research Network, 2012)
t(8;15)(q21;q21) NEDD4/RDH10 (Cancer Genome Atlas Research Network, 2012)
t(8;16)(p11;p12) KIAA0556/LSM1 (Cancer Genome Atlas Research Network, 2012)
t(8;16)(q22;q24) GSE1/NACAP1 (Cancer Genome Atlas Research Network, 2012)
t(8;21)(q11;q21) UBE2V2/NRIP1 (Cancer Genome Atlas Research Network, 2012)
t(9;9)(p21;p21) CDKN2A/FOCAD (Cancer Genome Atlas Research Network, 2012)
t(9;9)(p21;p13) PLAA/RUSC2 (Cancer Genome Atlas Research Network, 2012)
t(9;19)(p13;p13) FAM219A/S1PR5 (Cancer Genome Atlas Research Network, 2012)
inv(10)(p11q11) KIF5B/RET (Cai et al., 2013)
t(10;11)(q21;p15) CTNNA3/IGF2 (Cancer Genome Atlas Research Network, 2012)
t(10;11)(q22;q14) P4HA1/TRIM77P (Cancer Genome Atlas Research Network, 2012)
t(10;17)(q22;q12) SAMD8/LHX1 (Cancer Genome Atlas Research Network, 2012)
t(10;20)(q23;q13) WAPAL/PTPRT (Cancer Genome Atlas Research Network, 2012)
t(11;11)(p14;p13) EIF3M/MPPED2 (Cancer Genome Atlas Research Network, 2012)
t(11;11)(p11;q12) OR9Q1/OR4C46 (Cancer Genome Atlas Research Network, 2012)
t(11;11)(q12;q12) P2RX3/RTN4RL2 (Majewski et al., 2013)
t(11;11)(q12;q13) EEF1G/PPP6R3 (Cancer Genome Atlas Research Network, 2012)
t(11;11)(q12;q13) SHANK2/MS4A8B (Cancer Genome Atlas Research Network, 2012)
t(11;11)(q13;q22) PPP6R3/CNTN5 (Cancer Genome Atlas Research Network, 2012)
t(11;12)(p11;p13) ERC1/SPI1 (Cancer Genome Atlas Research Network, 2012)
t(12;20)(q12;q13) TAF4/ALG10B (Cancer Genome Atlas Research Network, 2012)
t(12;22)(q14;q12) SLC16A7/TTC28 (Cancer Genome Atlas Research Network, 2012)
t(13;20)(q12;p12) MACROD2/MPHOSPH8 (Cancer Genome Atlas Research Network, 2012)
t(14;14)(q11;q13) NPAS3/OXA1L (Cancer Genome Atlas Research Network, 2012)
t(14;14)(q12;q13) FOXG1/NPAS3 (Cancer Genome Atlas Research Network, 2012)
t(14;14)(q13;q21) MBIP/C14orf183 (Cancer Genome Atlas Research Network, 2012)
t(14;14)(q13;q21) SEC23A/IGBP1P1 (Cancer Genome Atlas Research Network, 2012)
t(16;16)(q12;q13) FTO/HERPUD1 (Majewski et al., 2013)
t(16;16)(q23;q24) JPH3/OSGIN1 (Cancer Genome Atlas Research Network, 2012)
t(16;22)(p12;q11) POM121L4P/LCMT1 (Cancer Genome Atlas Research Network, 2012)
t(17;17)(p13;p11) PIGL/RABEP1 (Cancer Genome Atlas Research Network, 2012)
t(17;17)(p11;q11) AKAP10/PSMD11 (Cancer Genome Atlas Research Network, 2012)
t(17;17)(p11;q11) KIAA0100/ALKBH5 (Cancer Genome Atlas Research Network, 2012)
t(17;17)(q23;q23) RPS6KB1/VMP1 (Majewski et al., 2013)
t(18;22)(q12;q11) CDC45/RIT2 (Cancer Genome Atlas Research Network, 2012)
t(19;19)(p13;p12) UNC13A/ZNF492 (Cancer Genome Atlas Research Network, 2012)
t(19;19)(q13;q13) BCL3/HIPK4 (Cancer Genome Atlas Research Network, 2012)
t(19;19)(q13;q13) SIPA1L3/CD22 (Cancer Genome Atlas Research Network, 2012)
t(19;21)(p13;q22) ITSN1/ZNF490 (Cancer Genome Atlas Research Network, 2012)
t(19;22)(p12;q11) MMP11/ZNF714 (Cancer Genome Atlas Research Network, 2012)
t(20;20)(q11;q13) ADNP/DLGAP4 (Cancer Genome Atlas Research Network, 2012)
t(20;22)(q11;q12) PISD/RBL1 (Cancer Genome Atlas Research Network, 2012)
t(22;22)(q11;q11) THAP7/PRODH (Cancer Genome Atlas Research Network, 2012)
t(22;22)(q12;q12) APOL3/ISX (Cancer Genome Atlas Research Network, 2012)
t(22;22)(q12;q12) MCM5/TOM1 (Majewski et al., 2013)

Note

Finally, 280 genes were found implicated in one translocation.

Bibliography

Pubmed IDLast YearTitleAuthors
233782512013KIF5B-RET fusions in Chinese patients with non-small cell lung cancer.Cai W et al
229607452012Comprehensive genomic characterization of squamous cell lung cancers.
229190032012Identifying and targeting ROS1 gene fusions in non-small cell lung cancer.Davies KD et al
236613342013Identification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing.Majewski IJ et al
191478282009EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues.Martelli MP et al
180831072007Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.Rikova K et al
250867252014FGFR1 amplification is associated with poor prognosis and smoking in non-small-cell lung cancer.Seo AN et al
176255702007Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.Soda M et al
235589532013Identification of targetable FGFR gene fusions in diverse cancers.Wu YM et al
250633152014Analysis of clinical characteristics and differential diagnosis of the lung biopsy specimens in 99 adenocarcinoma cases and 111 squamous cell carcinoma cases: utility of an immunohistochemical panel containing CK5/6, CK34βE12, p63, CK7 and TTF-1.Xu XY et al

External Links

Citation

Jean-Loup Huret

Lung: Translocations in Squamous Cell Carcinoma

Atlas Genet Cytogenet Oncol Haematol. 2014-10-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/6819/lung-translocations-in-squamous-cell-carcinoma