Intratumoral Genetic Heterogeneity in Rectal Cancer

Bettoni, Fabiana; Masotti, Cibele; Habr‐Gama, Angelita; Corrêa, Bruna; Gama-Rodrigues, Joaquim; Vianna, Maria Regina; Vailati, Bruna Borba; Julião, Guilherme P. São; Fernández, Laura Melina; Galante, Pedro A. F.; Camargo, Anamaria A.; Perez, Rodrigo Oliva

doi:10.1097/sla.0000000000001937

Cited by 52 publications

(25 citation statements)

References 10 publications

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“…However, it should be noted that we did not find any correlation between the copy number variation and mutation events. In accordance with the previous report [ 48 ], our results also suggest that a single biopsy is sufficient for determination of major copy number profiles and high-frequency mutations for target therapy, however, it is insufficient for precise detection of subclonal SCNAs and low-frequency mutations.…”

Section: Discussionsupporting

confidence: 92%

Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer

Liu

et al. 2017

BMC Cancer

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BackgroundColorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes. While colon cancer has been widely investigated, studies on rectal cancer are very limited. Here, we performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors.MethodsWe sequenced nine tumor regions and 88 single cells from two rectal cancer patients with tumors of the same molecular classification and characterized their mutation profiles and somatic copy number alterations (SCNAs) at the multi-region and the single-cell levels.ResultsA variable extent of genomic heterogeneity was observed between the two patients, and the degree of ITH increased when analyzed on the single-cell level. We found that major SCNAs were early events in cancer development and inherited steadily. Single-cell sequencing revealed mutations and SCNAs which were hidden in bulk sequencing. In summary, we studied the ITH of rectal cancer at regional and single-cell resolution and demonstrated that variable heterogeneity existed in two patients. The mutational scenarios and SCNA profiles of two patients with treatment naïve from the same molecular subtype are quite different.ConclusionsOur results suggest each tumor possesses its own architecture, which may result in different diagnosis, prognosis, and drug responses. Remarkable ITH exists in the two patients we have studied, providing a preliminary impression of ITH in rectal cancer.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3777-4) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer

Liu

et al. 2017

BMC Cancer

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“…Furthermore, there is intratumoral heterogeneity, which illustrates the danger of supporting a management strategy and predict pCR on a biopsy sample only. The São Paulo group studied this concept, and by looking at somatic mutations in different fragments of a same tumour, found that the majority of the mutations (60%) were present in only one fragment, with only 27% of mutations being expressed in all fragments [ 99 ]. Similarly, two rectal cancer patients with the same overall burden of disease can express different carcinoembryonic antigen (CEA) levels.…”

Section: What Is the Evidence That We Can Predict Response/risk Of Rementioning

confidence: 99%

Watch-and-Wait as a Therapeutic Strategy in Rectal Cancer

Bernier

Balyasnikova

Tait

et al. 2018

Curr Colorectal Cancer Rep

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Purpose of ReviewPathological complete response is seen in approximately one fifth of rectal cancer patients following neoadjuvant chemoradiation. Since these patients have excellent oncological outcomes, there has been a rapidly growing interest in organ preservation for those who develop a clinical complete response. We review the watch-and-wait strategy and focus on all aspects of this hot topic, including who should be considered for this approach, how should we identify treatment response and what are the expected outcomes.Recent FindingsThe major challenges in interpreting the data on watch-and-wait are the significant heterogeneity of patients selected for this approach and of methods employed to identify them. The evidence available comes mostly from retrospective cohort studies, but has shown good oncological outcomes, including the rate of successful salvage surgery, locoregional control and overall survival.SummaryThere is currently not enough and not robust enough evidence to support watch-and-wait as a standard approach, outside a clinical trial, for patients achieving clinical complete response following neoadjuvant chemoradiation. Furthermore, there is a lack of data on long-term outcomes. However, the results we have so far are promising, and there is therefore an urgent need for randomised control studies such as the TRIGGER trial to confirm the safety of this strategy.

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“…It was reported the DNA copy number alterations from individual glands of colorectal tumors showed striking spatial patterns, in which these changes are not distributed evenly across a tumor . A single biopsy may not represent the entirety of a tumor, as it was reported that three fragments derived from a single rectal adenocarcinoma tissue showed exclusive mutation profiles, and only 27% of the detected somatic point mutations were shared by all three fragments . It has been found in pancreatic cancer that genetic heterogeneity of metastatic pancreatic cancer resulted in proteome heterogeneity …”

Section: Intratumor Proteome Heterogeneitymentioning

confidence: 99%

Proteome Heterogeneity in Colorectal Cancer

Lim

2018

Proteomics

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Tumor heterogeneity is an important feature of colorectal cancer (CRC) manifested by dynamic changes in gene expression, protein expression, and availability of different tumor subtypes. Recent publications in the past 10 years have revealed proteome heterogeneity between different colorectal tumors and within the same tumor site. This paper reviews recent research works on the proteome heterogeneity in CRC, which includes the heterogeneity within a single tumor (intratumor heterogeneity), between different anatomical sites at the same organ, and between primary and metastatic sites (intertumor heterogeneity). The potential use of proteome heterogeneity in precision medicine and its implications in biomarker discovery and therapeutic outcomes will be discussed. Identification of the unique proteome landscape between and within individual tumors is imperative for understanding cancer biology and the management of CRC patients.

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Intratumoral Genetic Heterogeneity in Rectal Cancer

Cited by 52 publications

References 10 publications

Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer

Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer

Watch-and-Wait as a Therapeutic Strategy in Rectal Cancer

Proteome Heterogeneity in Colorectal Cancer

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