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Novel driver variants in the histone 3.3 genes, H3F3A and H3F3B, define bone and cartilage cancer sub-types

A selection of human cancers harbours somatic driver mutations in genes encoding histones, most notably childhood brain tumours with K27M substitutions of the histone 3.3 gene, H3F3A. We performed whole genome sequencing of the benign cartilage tumour, chondroblastoma, and targeted sequencing of histone 3.3 genes, H3F3A and H3F3B, in seven further skeletal tumour types. We identified an exceptionally high prevalence of novel histone 3.3 driver mutations at glycine 34 and at lysine 36. Histone 3.3 gene mutations were found in 91% in giant cell tumours of bone (48/53), mainly H3F3A G34W variants, and in 92% of chondroblastoma (73/79), predominantly K36M mutations in H3F3B. H3F3B is paralogous to the cancer gene H3F3A. However, H3F3B driver variants have not previously been reported in human cancer. Our observation demonstrate remarkable tumour-specificity of mutations, with respect to which histone 3.3 gene and residue is mutated, indicating that the advantage these mutations confer is tumour dependent. Moreover, tumour-specific mutation of H3F3A and H3F3B suggests, that although both genes encode identical proteins, they are likely non-redundant and employed differentially during skeletal development.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001000147 Cancer Genomics

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00000112994 bam 4.2 GB
EGAF00000112995 bam 4.7 GB
EGAF00000112996 bam 3.7 GB
EGAF00000112998 bam 3.7 GB
EGAF00000113000 bam 4.7 GB
EGAF00000114988 bam 5.3 GB
EGAF00000114990 bam 6.3 GB
EGAF00000114992 bam 5.4 GB
EGAF00000114993 bam 5.7 GB
EGAF00000114994 bam 5.5 GB
EGAF00000118112 bam 4.1 GB
EGAF00000118113 bam 4.7 GB
EGAF00000118114 bam 3.7 GB
EGAF00000118116 bam 3.7 GB
EGAF00000118118 bam 4.7 GB
EGAF00000118120 bam 4.0 GB
EGAF00000118121 bam 4.6 GB
EGAF00000118122 bam 3.6 GB
EGAF00000118124 bam 3.6 GB
EGAF00000118126 bam 4.6 GB
EGAF00000118128 bam 4.2 GB
EGAF00000118129 bam 4.7 GB
EGAF00000118130 bam 3.8 GB
EGAF00000118132 bam 3.7 GB
EGAF00000118134 bam 4.8 GB
EGAF00000118136 bam 4.1 GB
EGAF00000118137 bam 4.7 GB
EGAF00000118138 bam 3.8 GB
EGAF00000118140 bam 3.7 GB
EGAF00000118142 bam 4.8 GB
EGAF00000118144 bam 3.9 GB
EGAF00000118145 bam 4.4 GB
EGAF00000118146 bam 3.5 GB
EGAF00000118148 bam 3.4 GB
EGAF00000118150 bam 4.4 GB
EGAF00000118152 bam 4.0 GB
EGAF00000118153 bam 4.5 GB
EGAF00000118154 bam 3.6 GB
EGAF00000118156 bam 3.5 GB
EGAF00000118158 bam 4.5 GB
EGAF00000118160 bam 3.9 GB
EGAF00000118161 bam 4.4 GB
EGAF00000118162 bam 3.5 GB
EGAF00000118164 bam 3.5 GB
EGAF00000118166 bam 4.5 GB
EGAF00000118168 bam 4.0 GB
EGAF00000118169 bam 4.6 GB
EGAF00000118170 bam 3.7 GB
EGAF00000118172 bam 3.6 GB
EGAF00000118174 bam 4.6 GB
EGAF00000118183 bam 4.8 GB
EGAF00000118185 bam 5.6 GB
EGAF00000118187 bam 5.0 GB
EGAF00000118188 bam 5.2 GB
EGAF00000118189 bam 5.1 GB
EGAF00000118191 bam 5.1 GB
EGAF00000118193 bam 6.1 GB
EGAF00000118195 bam 5.4 GB
EGAF00000118196 bam 5.7 GB
EGAF00000118197 bam 5.5 GB
EGAF00000118199 bam 5.0 GB
EGAF00000118201 bam 5.9 GB
EGAF00000118203 bam 5.3 GB
EGAF00000118204 bam 5.5 GB
EGAF00000118205 bam 5.4 GB
EGAF00000118207 bam 5.2 GB
EGAF00000118209 bam 6.1 GB
EGAF00000118211 bam 5.5 GB
EGAF00000118212 bam 5.7 GB
EGAF00000118213 bam 5.6 GB
EGAF00000118215 bam 5.2 GB
EGAF00000118217 bam 6.1 GB
EGAF00000118219 bam 5.5 GB
EGAF00000118220 bam 5.7 GB
EGAF00000118221 bam 5.6 GB
EGAF00000118223 bam 5.3 GB
EGAF00000118225 bam 6.2 GB
EGAF00000118227 bam 5.6 GB
EGAF00000118228 bam 5.8 GB
EGAF00000118229 bam 5.7 GB
EGAF00000118231 bam 4.7 GB
EGAF00000118233 bam 5.4 GB
EGAF00000118235 bam 4.9 GB
EGAF00000118236 bam 5.1 GB
EGAF00000118237 bam 5.0 GB
EGAF00000118239 bam 4.5 GB
EGAF00000118241 bam 5.2 GB
EGAF00000118243 bam 4.8 GB
EGAF00000118244 bam 5.0 GB
EGAF00000118245 bam 4.8 GB
EGAF00000118247 bam 4.6 GB
EGAF00000118249 bam 5.3 GB
EGAF00000118251 bam 4.8 GB
EGAF00000118252 bam 5.0 GB
EGAF00000118253 bam 4.9 GB
EGAF00000118255 bam 4.6 GB
EGAF00000118257 bam 5.3 GB
EGAF00000118259 bam 4.8 GB
EGAF00000118260 bam 5.0 GB
EGAF00000118261 bam 4.9 GB
EGAF00000118263 bam 4.5 GB
EGAF00000118265 bam 5.2 GB
EGAF00000118267 bam 4.7 GB
EGAF00000118268 bam 4.9 GB
EGAF00000118269 bam 4.8 GB
EGAF00000118271 bam 4.7 GB
EGAF00000118273 bam 5.4 GB
EGAF00000118275 bam 4.9 GB
EGAF00000118276 bam 5.1 GB
EGAF00000118277 bam 5.0 GB
EGAF00000118279 bam 4.6 GB
EGAF00000118281 bam 5.3 GB
EGAF00000118283 bam 4.8 GB
EGAF00000118284 bam 5.1 GB
EGAF00000118285 bam 4.9 GB
EGAF00000118287 bam 4.7 GB
EGAF00000118289 bam 5.4 GB
EGAF00000118291 bam 4.9 GB
EGAF00000118292 bam 5.2 GB
EGAF00000118293 bam 5.0 GB
EGAF00000118295 bam 4.4 GB
EGAF00000118297 bam 5.1 GB
EGAF00000118299 bam 4.6 GB
EGAF00000118300 bam 4.8 GB
EGAF00000118301 bam 4.7 GB
EGAF00000118303 bam 4.4 GB
EGAF00000118305 bam 5.1 GB
EGAF00000118307 bam 4.6 GB
EGAF00000118308 bam 4.8 GB
EGAF00000118309 bam 4.7 GB
EGAF00000118311 bam 4.4 GB
EGAF00000118313 bam 5.2 GB
EGAF00000118315 bam 4.7 GB
EGAF00000118316 bam 4.9 GB
EGAF00000118317 bam 4.7 GB
EGAF00000118319 bam 4.6 GB
EGAF00000118321 bam 5.4 GB
EGAF00000118323 bam 4.9 GB
EGAF00000118324 bam 5.1 GB
EGAF00000118325 bam 5.0 GB
EGAF00000118327 bam 4.4 GB
EGAF00000118329 bam 5.2 GB
EGAF00000118331 bam 4.7 GB
EGAF00000118332 bam 4.9 GB
EGAF00000118333 bam 4.7 GB
EGAF00000118335 bam 4.4 GB
EGAF00000118337 bam 5.2 GB
EGAF00000118339 bam 4.7 GB
EGAF00000118340 bam 4.9 GB
EGAF00000118341 bam 4.7 GB
EGAF00000118343 bam 4.4 GB
EGAF00000118345 bam 5.1 GB
EGAF00000118347 bam 4.6 GB
EGAF00000118348 bam 4.8 GB
EGAF00000118349 bam 4.7 GB
EGAF00000118351 bam 4.6 GB
EGAF00000118353 bam 5.4 GB
EGAF00000118355 bam 4.9 GB
EGAF00000118356 bam 5.1 GB
EGAF00000118357 bam 5.0 GB
EGAF00000118360 bam 4.2 GB
EGAF00000118361 bam 4.8 GB
EGAF00000118362 bam 3.9 GB
EGAF00000118364 bam 3.8 GB
EGAF00000118366 bam 4.8 GB
EGAF00000118368 bam 4.0 GB
EGAF00000118369 bam 4.5 GB
EGAF00000118370 bam 3.6 GB
EGAF00000118372 bam 3.5 GB
EGAF00000118374 bam 4.5 GB
EGAF00000118376 bam 4.0 GB
EGAF00000118377 bam 4.5 GB
EGAF00000118378 bam 3.7 GB
EGAF00000118380 bam 3.6 GB
EGAF00000118382 bam 4.6 GB
EGAF00000118384 bam 3.9 GB
EGAF00000118385 bam 4.4 GB
EGAF00000118386 bam 3.6 GB
EGAF00000118388 bam 3.5 GB
EGAF00000118390 bam 4.5 GB
EGAF00000118392 bam 3.9 GB
EGAF00000118393 bam 4.5 GB
EGAF00000118394 bam 3.5 GB
EGAF00000118396 bam 3.5 GB
EGAF00000118398 bam 4.5 GB
EGAF00000118400 bam 3.9 GB
EGAF00000118401 bam 4.5 GB
EGAF00000118402 bam 3.6 GB
EGAF00000118404 bam 3.5 GB
EGAF00000118406 bam 4.5 GB
EGAF00000118408 bam 4.0 GB
EGAF00000118409 bam 4.5 GB
EGAF00000118410 bam 3.6 GB
EGAF00000118412 bam 3.5 GB
EGAF00000118414 bam 4.5 GB
EGAF00000118416 bam 4.0 GB
EGAF00000118417 bam 4.6 GB
EGAF00000118418 bam 3.7 GB
EGAF00000118420 bam 3.6 GB
EGAF00000118422 bam 4.6 GB
EGAF00000120224 bam 17.4 GB
EGAF00000120225 bam 2.4 GB
EGAF00000121327 bam 4.3 GB
EGAF00000121328 bam 4.9 GB
EGAF00000121329 bam 3.9 GB
EGAF00000121331 bam 3.8 GB
EGAF00000121333 bam 4.8 GB
EGAF00000121335 bam 4.3 GB
EGAF00000121336 bam 4.9 GB
EGAF00000121337 bam 3.9 GB
EGAF00000121339 bam 3.8 GB
EGAF00000121341 bam 4.8 GB
EGAF00000121343 bam 4.3 GB
EGAF00000121344 bam 4.9 GB
EGAF00000121345 bam 3.9 GB
EGAF00000121347 bam 3.8 GB
EGAF00000121349 bam 4.8 GB
EGAF00000121351 bam 4.3 GB
EGAF00000121352 bam 4.9 GB
EGAF00000121353 bam 3.9 GB
EGAF00000121355 bam 3.8 GB
EGAF00000121357 bam 4.8 GB
EGAF00000121359 bam 4.2 GB
EGAF00000121360 bam 4.8 GB
EGAF00000121361 bam 3.9 GB
EGAF00000121363 bam 3.7 GB
EGAF00000121365 bam 4.8 GB
EGAF00000121367 bam 4.2 GB
EGAF00000121368 bam 4.8 GB
EGAF00000121369 bam 3.9 GB
EGAF00000121371 bam 3.7 GB
EGAF00000121373 bam 4.8 GB
EGAF00000121375 bam 4.2 GB
EGAF00000121376 bam 4.8 GB
EGAF00000121377 bam 3.9 GB
EGAF00000121379 bam 3.7 GB
EGAF00000121381 bam 4.8 GB
EGAF00000121383 bam 4.4 GB
EGAF00000121384 bam 5.0 GB
EGAF00000121385 bam 4.1 GB
EGAF00000121387 bam 3.9 GB
EGAF00000121389 bam 5.0 GB
EGAF00000121390 bam 4.8 GB
EGAF00000121392 bam 5.6 GB
EGAF00000121394 bam 5.1 GB
EGAF00000121395 bam 5.3 GB
EGAF00000121396 bam 5.2 GB
EGAF00000121398 bam 4.6 GB
EGAF00000121400 bam 5.4 GB
EGAF00000121402 bam 4.9 GB
EGAF00000121403 bam 5.2 GB
EGAF00000121404 bam 5.0 GB
EGAF00000121406 bam 4.7 GB
EGAF00000121408 bam 5.5 GB
EGAF00000121410 bam 5.0 GB
EGAF00000121411 bam 5.2 GB
EGAF00000121412 bam 5.1 GB
EGAF00000121415 bam 4.8 GB
EGAF00000121416 bam 5.5 GB
EGAF00000121417 bam 4.5 GB
EGAF00000121419 bam 4.2 GB
EGAF00000121421 bam 5.4 GB
EGAF00000128167 bam 14.6 GB
EGAF00000128168 bam 18.3 GB
EGAF00000131413 bam 4.9 GB
EGAF00000131415 bam 5.7 GB
EGAF00000131417 bam 5.1 GB
EGAF00000131418 bam 5.3 GB
EGAF00000131419 bam 5.2 GB
EGAF00000131421 bam 4.8 GB
EGAF00000131423 bam 5.6 GB
EGAF00000131425 bam 5.0 GB
EGAF00000131426 bam 5.3 GB
EGAF00000131427 bam 5.1 GB
EGAF00000131429 bam 4.6 GB
EGAF00000131431 bam 5.3 GB
EGAF00000131433 bam 4.8 GB
EGAF00000131434 bam 5.0 GB
EGAF00000131435 bam 4.8 GB
EGAF00000131437 bam 4.8 GB
EGAF00000131439 bam 5.6 GB
EGAF00000131441 bam 5.0 GB
EGAF00000131442 bam 5.3 GB
EGAF00000131443 bam 5.1 GB
EGAF00000131445 bam 4.8 GB
EGAF00000131447 bam 5.6 GB
EGAF00000131449 bam 5.0 GB
EGAF00000131450 bam 5.2 GB
EGAF00000131451 bam 5.1 GB
EGAF00000131453 bam 4.7 GB
EGAF00000131455 bam 5.5 GB
EGAF00000131457 bam 4.9 GB
EGAF00000131458 bam 5.2 GB
EGAF00000131459 bam 5.0 GB
EGAF00000131498 bam 12.0 GB
EGAF00000131499 bam 1.9 GB
EGAF00000131501 bam 13.0 GB
EGAF00000131502 bam 2.1 GB
EGAF00000131504 bam 22.8 GB
EGAF00000131505 bam 3.6 GB
EGAF00000131507 bam 21.3 GB
EGAF00000131508 bam 3.3 GB
EGAF00000131510 bam 21.6 GB
EGAF00000131511 bam 3.4 GB
EGAF00000132170 bam 17.2 GB
EGAF00000152643 bam 28.3 GB
EGAF00000152644 bam 4.7 GB
EGAF00000152646 bam 28.6 GB
EGAF00000152647 bam 4.8 GB
EGAF00000152649 bam 9.6 GB
EGAF00000152650 bam 11.3 GB
EGAF00000152652 bam 10.7 GB
EGAF00000152653 bam 12.7 GB
EGAF00000152655 bam 10.8 GB
EGAF00000152656 bam 12.8 GB
EGAF00000152658 bam 5.6 GB
EGAF00000152659 bam 6.6 GB
EGAF00000152667 bam 44.3 GB
EGAF00000152670 bam 13.4 GB
EGAF00000152674 bam 9.4 GB
EGAF00000152675 bam 8.9 GB
EGAF00000161416 bam 9.9 GB
EGAF00000166054 bam 13.8 GB
EGAF00000166055 bam 13.0 GB
EGAF00000166056 bam 14.1 GB
EGAF00000166612 bam 22.0 GB
EGAF00000166991 bam 13.4 GB
EGAF00000166992 bam 12.5 GB
EGAF00000166994 bam 7.0 GB
EGAF00000166995 bam 6.5 GB
EGAF00000166996 bam 23.5 GB
EGAF00000171767 bam 42.1 GB
EGAF00000172188 bam 23.1 GB
EGAF00000180515 bam 18.7 GB
334 Files (2.0 TB)