Cancer Genome and Exome Sequencing in 2011

As a follow-up to my previous post, Disease-causing Mutations Discovered by NGS in 2011, I’ve attempted to compile cancer genome and exome sequencing studies published last year. For this compilation, I’ve emphasized publications in which whole-genome or exome sequencing was employed to multiple tumors or cancer cell lines, with the goal of identifying significantly altered genes or pathways in malignant cells. Even with these restrictions, the list of papers in 2011 was rather extensive. Links are provided to Pubmed for the citations; when a “key finding” is a link, it points to previous Massgenomics posts on the study. I’ve broken the publications down into several categories:

Cancer whole-genome sequencing
Exome sequencing of leukemia
Exome sequencing of carcinoma
Exome sequencing of melanoma
Pancreatic, gastric, and prostate cancer exomes

Whole-genome sequencing (WGS) studies

Several whole-genome sequencing studies of cancer were published last year. The largest of these was a study from the Broad Institute, in which whole-genome sequencing or exome sequencing was applied to 38 multiple myeloma tumors.

Cancer Whole-genome Sequencing
Cancer Type #Samples Key Finding(s) Publication
Myelodysplastic syndrome (MDS) 1 WGS
150 case
Recurrent mutations the U2AF1 splicing factor Graubert et al. Nat. Genet.
HCV+ Hepatocellular carcinoma 1 case Transcription-coupled DNA repair; several gene fusion events including BCORL1-ELF4 Wei et al. Nat. Genet.
Chronic lymphocytic leukemia 4 cases Recurrent mutations in NOTCH1, XPO1, MYD88, and KLHL6 Puente et al. Nature
Colorectal adenocarcinoma 9 cases Recurrent VTI1A-TCF7L2 fusions (3%) Bass et al. Nat. Genet.
Prostate cancer 7 cases Rearrangements disrupting CADM2, PTEN, or MAGI2 Berger et al. Nature
Multiple myeloma 22 WGS,
15 Exome,
1 both
Activating mutations in BRAF (4%) Chapman et al. Nature
Therapy-related AML 1 case Novel heterozygous 3-kilobase deletion affecting TP53 in germline DNA Link et al. JAMA
Non-Hodgkin lymphoma 14 cases
+113 RNA-seq
Frequent mutation of MLL2 (32%/89%) and MEF2B (11.4%/13.4%) in DLBCL/FL. Morin et al. Nature


Exome sequencing of leukemia

Several types of leukemia were characterized by exome sequencing, including chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), acute monocytic leukemia (M5 AML), and pediatric acute lymphocytic leukemia (ALL).

Exome Sequencing of Leukemia
Cancer Type #Samples Key Finding(s) Publication
CLL 105 cases Recurrent mutations of the splicing factor SF3B1 Quesada et al. Nat Genet 2011.
M5 AML 9 cases Somatic mutations of DNMT3A Yan et al. Nat Genet 2011.
AML (normal karyotype) 1 exome
553 case extension
Somatic mutations in BCOR Grossmann et al. Blood 2011.
Pediatric ALL 2 cases 4-7 somatic protein-altering mutations per case Lilljebjorn et al. Leukemia 2011.

Exome sequencing of carcinoma

Exome sequencing was also applied to many solid organ tumors, particularly carcinomas. The Cancer Genome Atlas research network published a landmark study of high-grade serous ovarian carcinoma, the first of several common cancers to be characterized by TCGA. A number of other TCGA efforts will likely see publication in 2012, including breast cancer, colorectal cancer, glioblastoma, and leukemia.

Exome Sequencing of Carcinoma
Cancer Type #Samples Key Finding(s) Publication
Serous ovarian 316 cases Recurrent mutations in TP53, NF1, BRCA1, BRCA2, RB1 and CDK12 TCGA, Nature 2011.
Head and neck squamous cell 74 cases Mutations in TP53, CDKN2A, PIK3CA, HRAS, and squamous differentiation genes. Stransky et al. Science.
Head and neck squamous cell 32 cases Mutations in TP53, CDKN2A, PIK3CA, and HRAS, FBXW7 and NOTCH1. Tumor-suppressor role for NOTCH1. Agrawal et al. Science 2011.
Renal carcinoma 7 cases Frequent mutation of the SWI/SNF complex gene PBRM1 Varela et al. Nature 2011.

Exome sequencing of melanoma

Melanoma was another cancer type surveyed by multiple exome sequencing studies in 2011. Interestingly, two studies of melanoma cell lines revealed frequent mutations in mitogen activated protein (MAP) kinase kinase [kinase] genes MAP2K1, MAP2K2, MAP3K5, and MAP3K9.

Exome Sequencing of Melanoma
Cancer Type #Samples Key Finding(s) Publication
Melanoma 14 cases Frequent mutations in GRIN2A Wei et al. Nat Genet. 2011.
Metastatic Melanoma 8 cell lines Mutations in MAP3K5 and MAP3K9 Stark et al. Nat Genet. 2011
Melanoma 7 cell lines Recurring somatic MAP2K1 and MAP2K2 mutations (8%) Nikolaev et al. Nat Genet. 2011

Pancreatic, gastric, and prostate cancer

Finally, I have a category of “other cancers” with exomes published in 2011; these include pancreastic cysts and cell lines, gastric cancer tumors, and prostate cancer samples derived through mouse xenograft models.

Pancreatic, Gastric, and Prostate Cancer Exomes
Cancer Type #Samples Key Finding(s) Publication
Pancreatic cancer 15 cell lines Genomic instability caused by MLH1 haploinsufficiency and complete deficiency Wang et al. Genome Res. 2011
Pancreatic neoplastic cysts 8 cyst resections Recurrent mutations in components of ubiquitin-dependent pathways Wu et al. PNAS 2011.
Gastric cancer 22 cases Frequent mutation of ARID1A Wang et al. Nat Genet 2011.
Prostate cancer 3 primaries
16 metastases
Recurrent alterations in TP53, DLK2, GPC6, and SDF4 Kumar et al. PNAS 2011

Conclusion and Outlook

Around 700 individual tumors representing 17 major cancer types were characterized in the studies above. That’s an astonishing number, but it’s only the tip of the iceberg. This year will see the publication of thousands or tens of thousands of cancer genomes/exomes. New genes and pathways will be identified. Mutational patterns will be revealed. Novel therapeutic targets will be suggested. I think that 2012 will be an exciting year for cancer genomics.

Ding L, Wendl MC, Koboldt DC, & Mardis ER (2010). Analysis of next-generation genomic data in cancer: accomplishments and challenges. Human Molecular Genetics, 19 (R2):R188-96. PMID: 20843826

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I like your website and articles! It's very helpful!

Mona Spector
Mona Spector

Hi Dan,

This is a great resource. Thanks for putting it together.

We have a paper published in Leukemia Dec 2011 on exome sequencing of a single case of mast cell leukemia. We found 2 somatic mutations that potentially impact therapeutic decisions for this rare form of leukemia.

Leukemia. 2011 Dec 16. doi: 10.1038/leu.2011.354.

I understand that you chose to limit the list to studies of multiple cases and our study does not fit that criteria. Just thought it would not hurt to ask if you would consider including our study in your compilation.



Dan Koboldt
Dan Koboldt

Ryan, absolutely! I enjoyed your paper and apologize for the oversight - thank you for the reminder.

Ryan Morin
Ryan Morin

Hi Dan.

Nice compilation. I am unarguably biased in this matter, but I wonder if our paper on non Hodgkin lymphoma could also merit inclusion in the WGS list. 12 cases sequenced by WGS, 2 by exome and a total of 113 extension cases (RNA-seq).

Key findings: Mutation of MLL2 in 89% of FLs and 32% of DLBCL and mutations in MEF2B in 11.4% of DLBCL and 13.4% of FL.




Morin, R.D., Mendez-Lago, M., Mungall, A.J., Goya, R., Mungall, K.L., Corbett, R.D., Johnson, N.A., et al., 2011. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature, 476(7360), pp.298–303.

Alfredo Hidalgo-Miranda
Alfredo Hidalgo-Miranda

Great compilation!! You can also include the paper about non-Hodgkin by Morin et. al. in Nature. 2011 Jul 27;476(7360):298-303. doi: 10.1038/nature10351.